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The Oxford Medicine 



BY VARIOUS AUTHORS 



VOLUME VT 



\ EDITED BY 

HENRY A. CHRISTIAN, A.M., M.D., LL.D., Sc.D. (Hon.), M.A.C.P., 
Hon. F.R.C.P. (Can.), D.S.jM. (A.M.A.) 

Hersey Professor of the Theory mid Practice of Physic, Emeritus, Harvard University 

SoTiietiine Clinical Professor of Medicine, Tufts College Medical School 

Sometime Visiting Physician, Beth Israel Hospital 

Physician-in-Chief, Emeritus, Peter Bent Brigl:am Hospital, Boston, Mass. 



NEW YORK 

OXFORD UNIVERSITY PRESS 

1949 






COPYRIGHT, 1921, 1923, 1924. 1925, 1926, 1927, 1928, 1929, 1930, 1931, 1932, 1933, 1934, 1935, 

1936, 1937, 1938, 1939. 1940. 1941, 1942, 1943, 1944, 1945, 1947, 1949 

BY THE OXFORD UNIVERSITY PRESS, INC. 



PRINTED IN THE UNITED STATES OF AMERICA 



CO-EDITORS 



BURGESS GORDON, AID. 

Clinical Professor of Medicine, Jefferson Medical College; Director and Pbysician-in- 

Chief, Barton MeiJiorial and White Haven Divisions, Jefferson Hospital, 

Philadelphia, Pennsylvania 



WILLIAM J. KERR, M.D. 

Professor of Medicine, University of California Medical School; Physician-in-Cbief, 
University of California Hospital, San Francisco, California 



CYRUS C STURGIS, AI.D. 

Professor of Medicine, University of Michigan; Director, Thomas Henry Sinipson 

Memorial Institute for Medical Research; Chairman, Department of 

Internal Medicine, University Hospital 



CONTRIBUTORS TO 
VOLUME \T 

N. S. ALCOCK, iMD. 

Director, Royal Coriizvall hifirvjary, Tniro, Evrrlcind. 

WALTER C. ALVAREZ, AI.D. 

Professor oj Medichie, Mayo Foundation, University of Minne- 
sota; Head of Section and Senior Covsidtaiit, Division of Medi- 
cine, Mayo Clinic, Rochester, Minn. 

A. GREIG ANDERSON, iM.D., F.R.C.P. (Lond.) 

Formerly Assistant Physician, Aberdeen Royal Infinnary, Aber- 
deen, Scotland. 

CARL DINGER, AI.D. 

Assistant Professor of Clinical Psychiatry, Cornell University 
Medical School; Associate Attendinir Phychiatrist, Next' York 
Hospital, Neu- York, N.Y. 

W. RUSSELL BRAIN, D.Al. (Oxf.), F.R.C.P. (Lond.) 

Physician, Royal London Ophthah/zic Hospital and Hospital for 
Epilepsy and Paralysis, Maida Vale; Neurologist, Mount Vernon 
Hospital, London, England. 

GOROWYN BROUN, AI.D. 

Professor of Lnternal Medicine, St. Louis University School of 
Medicine; Physician and Medical Director of the Oitt-Patient 
DepartTiient, St. Louis University Hospital Group; Consultant 
Physician, St. Lonis City Hospital, St. Louis, Mo. 

SIR E. FARQUHAR BUZZARD, Bart., K.C.V.O., AI.D., LL.D., F.R.C.P. 

(Lond.) 

Late Regius Professor of Medicine, University of Oxford; Late 
Extra-Physician to H. AL the King; Consulting Physician to 
St. ThoTiias's Hospital, London; I^ate Hon. Physician to the 
Radcliffe InfirTiiary, Oxford, England. 

HARRY CAAIPBELL, AI.D., B.S., F.R.C.P. (Lond.) 

Late Physician, Hospital for Diseases of Nervous System and 
West End Hospital, London?, England. 



HILDRED CARLILL, AI.D., M.A. (Cantal).) 

FoiiJicrly Physician to Wcsfmiiistcr Hospital and Lecti/rer on 
Diseases of the Nervous Systeni in the Medical School; SoTuethne 
Physician to the West End Hospital for Nervous Diseases, etc., 
London, En^rland. 

STANLEY COBB, M.D. 

Bidlard Professor of Netrropatholofry, Harvard University; Chief 
of Service, Psychiatry, Massachi/setts General Hospital, Boston, 
Mass. 

JAiMES COLLIER, M.D., B.Sc, F.R.C.P. (Lond.) 

Late Consnltino; Physician and Emeritus Lecttirer in Netrrolo^y, 
St. Geor^fe's Hospital; Late Senior Physician, National Hospital 
for Paralyzed and Epileptic, London, Ei/{rland. 

D. DENNY-BROWN, iVI.D., C.H.B., Dr. Pmi,., F.R.C.P. (Lond.) 

Professor of Neurology, Harvard University; Director, Neuro- 
logical Unit, Boston City Hospital, Boston, Mass. 

F. GOLLA, AI.D., F.R.C.P. (Lond.) 

Director of Burden Neurological Institute; Formerly Professor of 
Pathology of Mental Disorders, University of London; Director, 
Maudsley Hospital, London; Formerly Physician, Hospital for 
Epilepsy and Paralysis; ForTnerly Physician, St. George's Hos- 
pital, London, England. 

A. H. GORDON, ALD., C.iM., F.R.C.P. (Can.) 

Professor of Medicine, Emeritus, McGill University; Consulting 
Physician to the Montreal General Hospital, Montreal, Canada. 

G. PHILIP GRABFIELD, M.D. 

Formerly Instructor in Pharmacology, Harvard University; For- 
nierly Associate in Medicine, Peter Bent Brigham Hospital; 
Milton, Mass. 

SAMUEL B. GRANT, M.D. 

Instrttctor in Clinical Medicine, Washington University; Assis- 
tant Physician in Medicine, Barnes Hospital, St. Louis, Mo. 

BERNARD HART, M.D. 

Physician in Psychological Medicine, University College Hospital, 
London, and National Hospital, Queen's Square, London; Lec- 
turer in Psychiatry, University College Hospital Medical School, 
London, England. 



C AI. HINDS HOWELL, D.AL (Oxon.), F.R.C.P. (Lond.) 

Physician, National Hospital for Paralysis avd Epilepsy, Qiieeifs 
Square, Lo/hion; Consiiltiiig Physician, St. Bartholo7neiv's Hos- 
pital, London, England. 

REDVERS IRONSIDE iVI.B., F.R.C.P. (Lond.) 

Neurologist to West London Hospital; Physician, Hospital jar 
Paralysis and Epilepsy. Queen's Square, London; Physician to 
London Hospital, London, England. 

WILLIAM G. LENNOX, M.D., S.D. 

Assistant Professor of Net/rology and Secretary of Harvard 
Epilepsy Coimnission, Harvard University, Boston, Mass. 

WARFIELD T. LONGCOPE, M.D., LL.D., D.Sc. (Hon.) 

Professor of Medicine, ETiieritiis, Johns Hopkins University; 
Forvjerly Physiciai?-in-Chief, Johns Hopkins Hospital, Baltimore, 
Md.; CornhUl Faryn, Lee, Mass. 

SIR ASHLEY W. .MACKINTOSH, K.C.V.O., M.D., F.R.C.P. (Edin.) 

Late Evieritiis Professor of Medicine, Aberdeen University; Late 
Consulting Physician, Aberdeen Royal InfirTiiary, Aberdeen, 
Scotland. 

J. PURDON MARTIN, ALA., ALD., F.R.C.P. (Lond.) 

Neurologist, British Post-Gradiiate Medical School; Physician to 
Out -Patients, National Hospital for Nervous Diseases, Queen^s 
Square, London, England. 

DONALD AlcEACHERN, ALD. 

Biological Chemist, Montreal Neurological Institute; Lecturer in 
Nei/rology, McGill University, Montreal, Canada. 

H. HOUSTON AIERRITT, ALD. 

Professor of Clinical Neurology, College of Physicians and Sur- 
geons, Cohimbia University; Chief of Neiiropsychiatric Division, 
Montefiore Hospital, Ne^v York, N. Y. 

SIR FREDERICK W. AIOTT, K.B.E., ALD., LL.D., F.R.S., F.R.C.P. 

Late Pathologist to the London County Asyhmis and Director 
of the Pathological Laboratory; Late Physician to the Mandsley 
Neurological Hospital, Denmark Hill; Late Considting Physician 
to Charing Cross Hospital, London, England. 



DONALD iMUNRO, AI.D. 

Assistant Frofessor of Neiirolo(jrical Surgery, Harvard Unrcersity; 
Visiting Surgeon for Nei/roseirgery, Boston City Hospital, 
Boston, Mass. 

J. AI. NIELSEN, AI.D. 

Associate (Uinical Professor of Neurology, University of Southern 
California, Los Angeles, Cal. 

HAROLD D. PALAIER, AI.D. 

Late Associate in Psychiatry, Medical School, University of 
Pennsylvania: Late Psychiatrist to the Institute of the Pennsyl- 
vania Hospital, Philadelphia, Pa. 

WILDER PENFIELD, AI.D., D.Sc. (Oxox.), F.R.C.S. (Can.), F.R.C.S. 
(Lond.), F.R.S. 

Director, Montreal Neurological Institute; Professor of Neu- 
rology and Neurosurgery, McGill University, Montreal, Canada. 

TRACY J. PUTNAAl, AI.D. 

Formerly Professor of Nein'ology and Neurological Surgery, 
Colmiibia University; Formerly Director of Services of Neu- 
rology and Neurosurgery, Neurological Institute, Neiv York, 
N. Y.; Chief and Attending Surgeon, Department of Neuro- 
surgery, Cedars of Lebanon Hospital, Los Angeles, Cal. 

GEORGE RIDDOCH, AI.D., F.R.C.P. (Lond.) 

Physician and Director of Neurological Department to the 
London Hospital; Physician to Out-Patients, the Natioihtl Hos- 
pital for Nervous Diseases, Queen's Square, London, England. 

THURSTON D. RI\ ERS, AI.D. 

Assistant Psychiatrist, the Institute of the Pennsylvania Hospital, 
Philadelphia, Pa. 

T. A. ROSS, AI.D., F.R.C.P. (Edin.), F.R.C.P. (Lond.) 

l^ate Medical Director, Cassel Hospital of Functional Nervous 
Disorders, Sivayla//ds Pe//shurst, Kent, England. 

PERCY SAUNDERS, AI.B., F.R.C.P. (Lond.) 

Formerly Assistant Physician, National Hospital for Paralyzed 
and Epileptic and to the Royal Free Hospital, London, England. 



HARRY C. SOLOMON, iM.D. 

Professor of Psycbiatry, Hitrvcird Uni-versity: Medical Director, 
Boston Psychopathic Hospital, Boston, Mass. 

T. GRAINGER STEWART, M.D., F.R.C.P. (Lond.) 

Consulting Physician to the National Hospital for Paralysis and 
Epilepsy, Queen'' s Square, London; Formerly Considting Neu- 
rologist, West London Hospital; Consulting Neurologist to the 
Ministry of Pensions, London, England. 

EDWARD A. STRECKER, A.AI., M.D., Sc.D. (Hon.), Litt.D. (Hon.) 

Professor of Psychiatry, School of Medicine, University of Penn- 
sylvania; Chief of Clinic and Consultant to the Pennsylvania 
Hospital and the Institute of the Pennsylvania Hospital, Phila- 
delphia, Penn. 

H. CAMPBELL THOMSON, M.D., F.R.C.P. (Lond.) 

Formerly Consulting Physician to the I^epartnient for Nervous 
Diseases, Middlesex Hospital; Formerly Consulting Physician to 
the Hospital for Epilepsy and Paralysis, Maida Vale, England. 

L S. WECHSLER, ALD. 

Professor of Clinical Neurology, Columbia University; Attending 
Neurolo{>;ist and Chief of Service, Mt. Sinai Hospital, New York, 
N. Y. 

C. WORSTER-DROUGHT, i\LD., F.R.C.P. (Lond.) 

Consulting Physician in Neurology, Bethlehem Royal Hospital; 
Physician, West End Hospital for Nervous Diseases, London, 
Ejigland. 



ADDITIONAL CONTRIBUTORS TO 
VOLUME VI 

CHARLES BRENNER, M.D. 

Associate in Neurology, College of Fhysicimis and Surgeons^ 
Cohmibia University; Associate Attending Physician, Montefiore 
Hospital, Neiv York City. 

KEITH S. GRIAiSON, AI.D. 

Professor of Surgery, Duke University School of Medicine and 
Duke Hospital, Durham, North Carolina. 

GORDON E. HEIN, M.D. 

Clinical Professor of Medicine, University of Califorjiia; Chief 
of Medical Service, Veterans Hospital, San Francisco, Calif or?iia. 

JAMES C. REAVIS, M.D. 

Clinical Instructor in Medicine, University of California and 
Stanford University; Attending Physician, Veterans Administra- 
tioji Hospital, San Francisco, Calif or?iia. 

ROBERT F. WATSON, M.D. 

Associate Professor of Medicine, Cornell University Medical 
College; Attending Physician, New York Hospital, Chief -of - 
Service, The Vincent Astor Diagnostic Service, New York City. 



CONTENTS OF VOLUME Vl 

CHAPTER I PAGE 

ANATOAIICAL AND PHYSIOLOGICAL INTRODUCTION TO DISEASES 

OF THE NER\X)US SYSTEAl . . , i 

By J. M. Nielsen 

CHAPTER I- A 

ELECTROENCEPHALOGRAPHY 46(7) 

By W'liJ.iAM G. Lennox 

CHAPTER II 

X'ASCULAR DISTURBANCES 47 

By E. Farouhar Bv/.ZARn 

CHAPTER II-A 

CEREBRAL ARTERIOSCLEROSIS WITH REPEATED THROMBOSIS 

OF SMALL INTRACRANIAL ARTERIES . . . . . . 68(1) 

By Walter C. Alvarez 

CHAPTER III 

ENCEPHALITIS AND O I HER \1RUS INFECTIONS *OF CENTRAL 

NER\'OUS S^STEAI 69 

By Gorowyn O. Broun 

CHAPTER III-A 
POST- VACCINAL ENCEPHALITIS 84(3) 

By a. H. Gordon 

CHAPTER I\^ 

BRAIN ABSCESSES 85 

By C. M. Hinds Howell 

CHAPTER V 
CRANIO-CEREBRAL INJURIES 99 

By Donald AIunro 



xii CONTENTS 

CHAPTER VI PAGE 

INTRACRANIAL TUMOURS 137 

Bv WiLUER Penfield anh Donald McEachern 

CHAPTER VII 

DIPLEGIA 217 

By a. Greig Andikson 

CHAPTER VIII 

HYDROCEPHALUS 223 

By a. Greu; Anderson 

CHAPTER IX 

IDIOCY 233 

By a. Grek; Anderson 

CHAPTER X 

APHASIA 243 

By J. .\i. Nieesen 

CHAPTER XI 
DISEASES OF THE BASAL GANGLIA AND SUBTHALAMIC NUCLEI . 261 

By D. Denny-Brown 

CHAPTi R XII 

LESIONS OF THE MIDULLA OBLONGATA 303 

By George Riddoch 
Revised by' J. Purdon Martin 

CHAPTER XIII 
DISEASES OF THE CERIBRAl. MENINGES 309 

Bv H. Ca.mphele Thomson 

CHAP! IK XI\^ 

IM RINSIC DISEASES OF 1 HE SPINAL CORD 327 

By James Collier 
Revised r.v \\ . Ri ssi li. Brain 



CONTEXTS xiii 

CHAPTER X\' PAGE 

INTRINSIC DISEASES OF FHE SPINAL CORD (Continued) . . . .391 

By JA.MES Collier 

CHAPTER XVI 

TUMORS OF THE SPINAL CORD AND OFHER LESIONS CAUSING 

COMPRESSION 447 

By \\ . Russell Brain 

CHAPTER XMI 

TRAUMATIC AFFECTIONS OF THE SPINAL CORD 471 

By N. S. Alcock 

CHAPTER X\ 111 
LESIONS OF THE CAUDA EQUINA AND CONUS MEDULLARIS . . 483 

By Georce Riodoch 
Revised by J. Purdon Mar 1 in 

CHAPTER XIX 
SYPHILIS OF THE NI R\()US SYSTEM 493 

Bv Sir Frederick W. Mott 
Revised and partly rewritten ry C. \\ Oksier-Drolcht 

CHAPTER XX 
TABES DORSALIS 559 

By Sir Frederick \\ . Mon 

Re. ISLD AND PARILY REWRITTEN BY C \A t)RS ! KR-DuoL (.HT 

CHAPTER XXI 

DEMENTIA PARALYTICA (PARETIC NEUROSYPHILIS) . . . .591 
By H. Houston Mi.rrut and HAiun C. Solomon 

CELAPTER XXii 
DISEASE OF THE NER\()US SYSTEM IN CONGENI lAL SYPHILIS . . 617 

By C. W'orsier-Drought 

CHAPTER XXIII 
DISSEMINATED SCLEROSIS AND ENCEPHALOMYELl I IS .... 625 

By IrACY J. PUTNA.M 



xiv CONTENTS 

CHAPTER XX I \' ' PACK 

.MULTIPLE NEURITIS AND NEUROPATHY 647 

By I. S. Wechsler 

CHAPTER XXV 

CRANLAL NER\E PALSIES 675 

By Hildred Carlill 

CHAPTER XXVI 
PARALYSIS OF SPINAL NER\ ES 709 

By GEORCiK RiDDOCH 
ReVISEU HV J. PURDON MaRTIN 

CHAPTER XX\ II 

THE NEURALGIAS 747 

B^ HARR^ Campbell 

CHAPTER XXMII 

THE TROPHIC LESIONS 781 

By Harry Campbell 

CHAPTER XX\ Ill-A 

SCLERODERMA 828(1) 

Bv \\ arfieli) T. Lon(.cope 

CHAPTER XXIX 
THE \EGETATIVE NERX'OUS SYSTEM 829 

By Grainc.er Siewart 

CHAPTER XXX 
EPILEPSY 893 

By Sianleii Cobb and \\ 11 i iam G. Lennox 

CHAP! ER XXXI 
HEADACHE 917 

By \\'alter C. Alvarez 



CONTENTS XV 

CHAPTER XXXI-A page 

MIGRAINE 936(5) 

By Walter C. Alvarez 

CHAPTER XXXII 

CHOREAS 937 

By Ashley A\'. Macklmosh and A. C^reig Anderson 

CHAPTER XXXIII 
THE DYSTROPHIES AND ALLIED DISORDERS OF MUSCLES . . .971 

By Reovers Ironside 

CHAPTER XXXIIl-A 

PSYCHOANALYSIS 998(63) 

By Carl Binger 

CHAPTER XXXIV 

HYSTERIA 999 

B^ F. Golla 

CHAPTER XXXV 

NEURASTHENIA 1027 

By T. a. Ross 

CHAPTER XXXVI 

PSYCH ASTHENIA 1045 

By Bernard Hart 

CHAPTER XXXVII 

OCCUPATION NEUROSES 1065 

By Perc;y Saunders 

CHAPTER XXX\ 11-A 

ALCOHOLIC INTOXICATION AND ALCOHOLISM .... 1086(1) 

B^ Edward A. Sikeckek and Ihurston D. Rivers 

CHAPTER XXXMI-B 

DRUG ADDICTION 1086(25) 

By Harold D. Palmer 

CHAPTER XXXVIII 

DISORDERS OF SLEEP 1087 

By Percy- Saunders 



xvi CONTENTS 



CHAPTER XXXIX page 

TETANY "oi 

By Samuel B. Grant 

CHAPTER XL 
SPINAL FLUID IN DIAGNOSIS m? 

By G. p. Grabfield 



ADDITIONAL CONTENTS OF \ OLUME Vl 

CHAPTER III 

ENCEPHALITIS AND OTHER MRUS INFECTIONS OF THE 

CENTRAL NER\'OUS SYSTEM 69 

By Goronwy O. Broun 

CHAPTER MA 

MULTIPLE NEUROFIBROAL\TOSIS 216(45) 

By Gordon E. Hein and James C. Reams 

CHAPTER XMII 

LESIONS OF THE CAUDA EQUINA AND CONUS MEDUTLLARIS . . 483 

By N. S. Alcock 

CHAPTER XXIX 

THE AUTONOAIIC NERVOUS SYSTEM 829 

By Keith S. Gri.mson 

CHAPTER XXXII 

SYDENHAM'S CHOREA 937 

By Robert F. Watson 

CHAPTER XL 

THE CLINICAL EXAMINATION OF THE CEREBROSPINAL FLUID . 1117 
By Charles Brenner and H. Houston Merritt 



ILLUSTRATIONS 

CHAPTER I {Anatomical and Physiological Introduction to Diseases of the Nervous 
System) 

FIG. PAGE 

1. Diagram of a simple spinal reflex. (Courtesy of Edward Arnold, Pub.) Facing 4 

2. Diagram of some of the Impulses controlling the Anterior Cornual Cell. 

A = Inter-segmental Reflex Control. 
R-S = Rubro-spinal. Synergic Control. 
T-S = Tecto-spinal. Reflex Visuo-motor Control. 

V-S = Vestibule-spinal. Equilibratory control and contractile muscle tonus. 
P-S = Ponto-spinal. Plastic muscle tonus. 
D-R = Dentato-rubral path. 

E = Automatic Associated Movements. 
E = Striato-rubral path. 

S = Striato-reticular path, inhibiting plastic tonus. 
Py = Pyramidal Voluntary Motor path. 

Note. — "The nerve cell from which the white ramus is derived should lie 
in the lateral cornu, i.e., behind the anterior cornual cell and not in front of 
it, as shown in the diagram." Facing 8 

3. Diagram of chief sensory tracts in spinal cord, medulla, pons and cerebrum. 

(Courtesy of Edward Arnold, Publisher.) Facing 16 

4. Scheme of Cerebral Localization (outer surface.) Facing 18 

5. Scheme of Cerebral Localization (mesial surface.) (Courtesy of Edward 

Arnold, Publisher.) Facing 18 

6. Diagram of Pyramidal tract and its course through the brain and cord . 21 

7. Horizontal section through right cerebral hemisphere, showing position of 

the various strands in the internal capsule. (Modified from Beevor and 
Horsley.) 22 

8. Corticospinal and subcorticospinal tracts. 

A, Crossed pyramidal tract; 

B, Direct pyramidal tract; 

1, Rubrospinal tract; 

2, Tectospinal tract; 

3, Vestibulospinal tract. 

(Courtesy of Edward Arnold, Publisher.) Facing 24 

9. Vertical mesial section through cerebellum, pons and medulla . Facing 26 

10. Cerebellum: Upper surface. (Courtesy of Edward Arnold, Publisher.) Facing 26 

11. Cerebellum: Posterior surface Facing 26 

12. Cerebellum: antero-inferior or ventral surface. (Courtesy of Edward 

Arnold, Publisher.) Facing 26 

13. Horizontal section through cerebellum 27 

14. Cerebellipetal and cerebellifugal paths. (Courtesy of Edward Arnold, 

Publisher.) Facing 28 

Vol.6. 1231 XV 



xvi ILLUSTRATIONS 

FIG. PAGE 

15. Diagram of Visual Paths (Modified from Vialet). 
Lesion at i. produces Blindness of one eye. 
Lesion at 2. produces Bi-temporal heniianopia. 
Lesion at 3. and 3. produces Bi-nasal heniianopia. 

Lesion at 4. produces R. hemianopia with hemiopic pupil reaction. 

Lesion at 5. produces R. hemianopia with normal pupil reaction. 

Lesion at 6. produces R. hemianopia with normal pupil reaction. 

Lesion at 7. produces Loss of visual orientation and localization in space. 

Lesion at 8. produces Word-blindness. (Courtesy of Edward Arnold, 

Publisher.) Facing 36 

16. Diagram of trigeminal, facial and glossopharyngeal nerves, showing course 

of taste fibers. (Courtesy of Edward Arnold, Publisher.) . Facing 38 

17. Diagram of connections of cochlear and vestibular nerves 38 

18. Arteries at the base of the brain. One, the lenticulo-striate, is called the 

artery of cerebral hemorrhage. (After Dercum.) 40 

19. Diagram of arterial supply of cortex. (Courtesy of Edward Arnold, Pub- 

lisher.) Facing 40 

20. Arterial supply of basal ganglia and cortex. (After Beevor.) 41 

21. Diagram of the course and distribution of the terminal arteries of the spinal 

cord. (After Van Gehuchten.) (Courtesy of Edward Arnold, Pub- 
blisher.) Facing 44 

22. Diagram illustrating connections between a sympathetic ganglion and a 

spinal nerve in the thoracico-abdominal region 46 

23. The vegetative, nervous system, with its autonomic and sympathetic subdi- 

visions. In the sympathetic, each nerve cell (S) has an adrenal secretory 

cell (A) in connection with it. (Courtesy of Edward Arnold, Pub.) Facing 46(2) 



CHAPTER II (Vascular Disturbances) 

FIG. 

1. Section of middle cerebral artery showing arteritis, throinbosis and organiza- 

tion of the thrombus SI 

2. Section of a brain showing areas of softening in both hemispheres caused by 

gummatous arteritis of both middle cerebral arteries 53 

3. A brain showing the various results of cerebral thrombosis 54 

4. Section of a brain with widespread atheroma of the arteries 55 

5. Section of a brain showing a hemorrhage in the lenticular region ... 56 

6. Hemorrhage into the subarachnoid space at the base of the brain and spread- 

ing down the surface of the spinal cord 57 



CHAPTER III (Encephalitis) 

FIG. 

1. Microphotograph of cortex of brain in a case of encephalitis lethargica, 

showing round cells in adventitial sheath of blood vessel, and two 
petechial hemorrhages 7^ 

2. Microphotograph of cortex of brain in a case of encephalitis lethargica, 

showing chain of small round cells along the walls of a capillary vessel, 

and neurophagia of nerve cells 77 

Vol. 6. 1231 



ILLUSTRATIONS xvli 

CHAPTER IV {Brain Abscesses) 

FIG. PAGE 

1. Showing case of acute brain abscess, opened by operation 87 

2. Showing case of chronic abscess of brain in temporosphenoidal lobe ... 88 

3. Clinical chart of case of right sided subcortical abscess, which ruptured into 

lateral ventricle 91 

CHAPTER V {Cerebral Injuries) 

FIG. 

I. Colored diagrammatic scheme to illustrate the circulatory changes accom- 
panying an intracranial (subdural) hemorrhage .... Facing 104 

CHAPTER XHI {Diseases of the Cerebral Meninges) 
FIG. 

1. Diagram showing positions suitable for lumbar puncture 311 

2. Showing method of obtaining Kernig's sign 317 

3. Case of posterior basic meningitis showing extreme retraction of the head . 324 

CHAPTER XIV {Intrinsic Diseases of the Spinal Cord) 

FIG. 

1. Sections of the spinal cord and medulla from a case of progressive muscular 

atrophy, stained by the Weigert-Pal method 331 

2. Sections of the spinal cord from a case of subacute combined degeneration 

with pernicious anemia in which the degeneration is confined to the 
posterior columns 359 

3. Sections of the spinal cord from a case of subacute combined degeneration 

before the degeneration has advanced beyond the posterior and lateral 
regions 359 

4. Sections of the spinal cord and medulla from a long standing case of subacute 

combined degeneration 360 

5. Charts of the sensory loss from a case of subacute combined degeneration, 

showing the progressive loss as the disease advances 364 

6. Section of the lumbar spinal cord from a case of poliomyelitis .... 373 

7. Section of the ventral horn from the lumbar cord from a case of rapidly fatal 

poliomyelitis, stained with hematoxylin 374 

8. Sections of the ventral horn from a recent case of poliomyelitis, stained with 

hematoxylin 375 

9. Similar section in which blood vessels are seen in transverse section showing 

lymphocyte cuffing and general lymphocytic exudation 376 

10. Another section in which blood vessels with lymphocyte cuffing are seen in 

longitudinal section 377 

11. Section of a muscle which had been partly paralyzed, from a case of polio- 

myelitis of some standing 378 

CHAPTER XV {Intrinsic Diseases of the Spinal Cord, Continued) 

FIG. 

1. Sections of the spinal cord and medulla from a case of syringomyelia . . 394 

2. Section of the medulla from a case of syringomyelia 395 

3. Section of the cervical spinal cord from a case of Friedreich's disease . . 410 

Vol.6. 1231 



xviii ILLUSTRATIONS 

CHAPTER XVIII (Lesions of the Cauda Equina and Conus Medullaris) 

FIG. PAGE 

1. Complete cauda lesion: to represent the area of sensory loss 486 

2. Showing area of over-reaction to pin prick; also area in which skin was in- 

sensitive to light touch, pin prick, heat and cold 487 

3. Area of anaesthesia and analgesia in a case in which the first, second, third, 

and fourth lumbar roots on the left side were injured by a rifle bullet . 488 

4. Showing the extent of the sensory loss when the fifth lumbar, first and fourth 

and fifth sacral roots on the right side were injured by a piece of shell. 489 

5. Area representing the extent of the anaesthesia and analgesia following injury 

of all the sacral roots 490 

6. Showing area of sensory loss when the second, third, fourth and fifth sacral 

roots on the right side, and the fourth and fifth sacral roots on the left 
side, were injured 491 

CHAPTER XXI {General Paresis) 
FIG. 

1. Spirocheta pallida in the frontal cortex of a case of general paralysis, illustrat- 

ing the disseminated type of spirochetosis in which the organisms are 
quite evenly scattered throughout the parenchyma 596 

2. Jahnel's "bee-swarm" type of spirochetosis found in association with the 

peri-vascular lesion 597 

3. A portion of Figure 2 showing in detail the spirochete-entanglement and the 

difficulty in representing the single organism in one focal plane when they 
occur in enormous numbers 598 

CHAPTER XXIII [Disseminated Sclerosis) 

FIG. 

1. Serial sections, stained by Weigert-Pal method, showing patches of sclerosis 

in the region of the medulla in a case of disseminated sclerosis . . 628 

2. Longitudinal sections, stained by Weigert-Pal method, of the spinal cord, 

showing patches of sclerosis in a case of disseminated sclerosis . 628 

3. Section of medulla, stained by Weigert-Pal method, showing a patch involv- 

ing the fillet and olive on the left side and a patch on the floor of the 
fourth ventricle on the opposite side. The ventral patch shows incom- 
plete demyelination 629 

4. Optic chiasma, stained by Weigert-Pal method, showing patches on the left 

optic nerve, left side of chiasma and left optic tract. The inner part 

of the crura cerebri and anterior pillars of the fornix are clearly seen 631 

5. Longitudinal section of the optic nerve, stained by the Weigert method, 

showing three patches of disseminated sclerosis, one reaching to within 
a few millimetres of the disc head. (Reproduced by the kind permission 
of Dr. Gordon Holmes.) 632 

6. Microphotograph of the edge of a recent disseminated patch showing peri- 

vascular infiltration in the wall of two vessels, passing downward to- 
wards nerve tissue 633 

CHAPTER XXV (Cranial Nerve Palsies) 

FIG. 

la. Indirect examination of the left fundus 680 

lb. E.\amination of the right fundus 680 

Vol.6. 1231 



ILLUSTRATIONS xix 

FIG. PAGE 

2. Left third nerve palsy, showing ptosis 682 

3. Showing dilated pupil and paralysis of upward movement 682 

4. Showing paralysis of downward movement 682 

5. Showing palsy of internal rectus on left 682 

6. Showing that left external rectus is unaffected 684 

7. Bilateral ptosis with frontalis overaction 684 

8. Congenital ptosis 684 

9. Bilateral palsy of internal recti; divergent strabismus 684 

10. Left facial palsy 685 

11. Left facial palsy followed by bilateral third nerv-e palsy 686 

12. Bilateral third nerve palsy . " 687 

13. Showing recovery of bilateral third nerve palsy and of palsy of left seventh 

nerve 688 

14. Showing exaggeration of the normal comparative anaesthesia of the ocular 

conjunctiva, in a case of hysteria 689 

15. Paralysis of the left fifth nerve; the jaw is deviated to the left side . . . 690 

16. Palsy of the left external rectus 691 

17. Showing swelling of the face with left facial palsy 693 

18. Left facial palsy, with contractures 694 

19. Congenital bilateral facial palsy 695 

20. Herpes auris 696 

21. Showing paralysis of left trapezius 705 

22. Paralysis of left trapezius, showing rhomboids and displacement of scapula. 705 

23. Congenital torticollis, with facial asymmetry 706 

24. Atrophic palsy of right side of tongue, with deviation on protrusion . . . 707 

CHAPTER XX\'I {Paralysis of Spinal Nerves) 

FIG. 

1. Showing area of loss of sensibility in upper arm, to light touch and pin prick 

which followed di\'ision of the posterior roots 715 

2. Showing the effect of shaving the skin on the side of the area of insensibility 

to light touch after division of the musculospiral nerve in the arm . . 716 

3. Area of insensibility to light touch following division of the circumflex nerve 730 

4. Showing area of anaesthesia and that of total loss of sensibility to pin prick 

following division of the right musculospiral nerve in the middle of the 

arm 732 

5. Area of cutaneous sensory loss which followed division of the median nerve in 

the arm 734 

6. Area of total cutaneous insensibility in hand; also area of loss to light touch 

following div'ision of the ulnar nerve 735 

Area of complete insensibility to all stimuli following division of the sciatic 

nerve trunk 737 

Areas of loss to light touch and pin prick after section of the external popliteal 

nerve below the origin of the lateral cutaneous branch 738 

.Areas insensitive to pin prick and to light touch after division of the external 

popliteal nerve above the origin of its lateral cutaneous branch . 739 
10. Extent of cutaneous insensibility after division of the internal popliteal nerve 

in the lower third of the thigh 740 



Vol.6. 1231 



XX ILLUSTRATIONS 

CHAPTER XXX'II {The Neuralgias) page 

FIG. 

1. Diagram showing the algenic tract 748 

2. Diagram showing the connection between a spinal protoneurone and a spino- 

thalamic neurone subser\^ing pain sensibility 749 

3. Diagram showing the connections of a spinal protoneurone with a pregan- 

glionic neurone 749 

4. Diagram showing Head's dorsal areas of the scalp 755 



CHAPTER XXIX {The Vegetative Neroous System) 

FIG. 

1. Diagrammatic representation of the general scheme and distribution of the 

vegetative nervous system {colored) 833 

2. Diagram showing motor and sensory columns in connection with the vege- 

tative system 838 

3. Showing a voluntary motor neuron sending its axon into a spinal ner\e via a 

spinal root, and two sensory peripheral neurons with their neurosomes 
(cell bodies) in a spinal root ganglion 842 

4. Showing the exit of the sympathetic strands from the central nervous system, 

and their relation to the ganglia of the sympathetic cords and the spinal 
ner\'es 844 

5. Diagram to show the connector fibres and excitor neurons of the urogenito- 

dermal system in the female 846 

6. Showing the cranial autonomic fibres leaving the brain by the third, seventh, 

ninth and tenth nerves 847 

7. Showing the parasympathetic fibres pertaining to the sphenopalatine, sub- 

maxillary, sublingual and otic ganglia 848 

8. Showing the parasympathetic fibres from the superior and inferior salivary 

nuclei leaving the brain by the seventh and ninth nerves .... 849 

CHAPTER XXXHI {The Myopathies and Allied Conditions) 
FIG. 

1. Pseudo-hypertrophic myopathy. .Microphotograph of cross section of a 

portion of gastrocnemius showing large and astrophic muscle fibres and 
connective tissue hyperplasia 975 

2. Pseudo-hypertrophic myopathy. Mode of rising 977 

3. Pseudo-hypertrophic myopathy. Method of producing extension of the 

thighs 978 

4. Myopathic facies showing wide palpebral fissures and projecting lips in 

facio-scapulo-humeral myopathy 982 

5. Atrophic myopathy showing atrophy of the sternal portion of the pectoralis 

major. Note also the projection of the scapulae above the shoulders . 983 

6. The same patient showing winging of the scapulae 984 

7. Atrophic myopathy. " Wasp-waist " deformity 985 

8. Amyotonia congenita 991 

9. Amyotonia congenita 992 

10. The foot in amyotonia congenita showing the projecting os calcis and the 

rounded sole 993 

11. Difftculty in opening the eyes after voluntary closure of the lids in myotonia 997 

12. Rigid facies of myotonia 998 

Vol. 6. 1231 



ILLUSTRATIONS xxi 

FIG. PAGE 

13. Myotonia congenita. Myotonic dimpling in the deltoid (indicated by arrow) 

after direct percussion 998(1) 

14. Myotonia congenita showing the hypertrophied muscles 998(2) 

15. Transverse section of the cervical cord in peroneal muscular atrophy show- 

ing degeneration (White stippling) in the columns of GoU .... 998(5) 

16. Peroneal muscular atrophy 998(6) 

17. Lymphorrhage in the biceps muscle 998(19) 

18. Complete external ophthalmoplegia in myasthenia gravis with double ptosis 

and weakness of the jaw muscles. The jaw is characteristically sup- 
ported by the hand 998(21) 

19. The myasthenic smile. Note the tilting of the head to compensate for the 

double ptosis 998(22) 

20. Idiopathic tetany showing the attitude of the hands and Uffenheimer's 

"carp-mouth" 998(28) 



Vol.6. 1231 



CHAPTER I 

ANATOMICAL AND PHYSIOLOGICAL INTRODUCTION TO 
DISEASE OF THE NERVOUS SYSTEM 

By J. M. NIELSEN 

Table of Contents 

Neuron Doctrine 2 

Reflex Arc " . ^ 

Types of Spinal Reflexes 5 

Flexor Reflex 5 

Stretch Reflex 6 

Intersegmental Reflexes 7 

Final Common Pathway 7 

Lesions of the Lower Motor Neuron 9 

Lower Sensory Neuron 9 

Gross Anatomy of the Spinal Cord 12 

" Centers" in the Spinal Cord 17 

Medulla Oblongata 19 

Pons 22 

Cerebellum 22 

Mesencephalon 26 

Vegetative Nervous System 28 

Communicantes Vegetative Nervous System within the Spinal Cord . . . .31 

Vegetative Nervous System within the Medulla Oblongata ^^ 

Diencephalon ' ^^ 

Hypothalamus t,^ 

Thalamus 37 

Subthalamus 38 

Corpus Striatum 38 

Pallium 42 

Occipital Lobe 44 

Temporal Lobe 46 

Parietal Lobe 46 (i) 

Frontal Lobe . 46 (i) 

Circulation of the Brain 46 (4) 

Anatomical Basis of Memory 46 (6) 

Neurological Basis of Psychiatry 46 (6-2) 

Spontaneous Ekctrical Activity of the Cortex 46 (6-3) 

Bibliography 46 (6-5) 

COPYRIGHT 1945 BY THE OXFORD UNIVERSITY PRESS, NEW YORK, INC. 



2 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

The following outline of the anatomy and physiology of the nervous system 
is to be regarded merely as a statement of the fundamentals, which are necessary 
equipment to an understanding of the diseases affecting it. An attempt is made 
to present what may be called the present general concept without entering into 
the history of its development. 

Neuron Doctrine 

A basic concept of the neurophysiology is the neuron doctrine which originated 
with His and Forel and ripened with Ramon y CajaP and Waldeyer; the last 
named gave the neuron its name. The neuron doctrine states that the unit of 
neural function is the neuron or ganglion cell with its dendrites and axon and that 
all processes of the cell end without anastomosis or continuity with any other nerve 
cell but terminate by contiguity. 

A neuron consists of a cell body or perikaryon, filled with nucleus, nucleolus 
and many ramifying fibrils and processes of two types, dendrites which receive 
afferent impulses carried to the cell and an axon which transmits efferent impulses 
from the cell to another nerve cell or to an effector organ. Normally impulses 
travel in only one direction. The points of contact between two neurons is known 
as a synapse; the terminal fibrils of the axon have " end feet " or buttons, boutons 
terminaux. which contact the perikaryon or the dendrites of another neuron. The 
neurons are held in a neuroglial mass of cells of three general types, astrocytes, 
oligodendroglia and microglia cells. 

The neurons are the conductors of the nerve impulses; the astrocytes are 
attached with " sucker feet " to capillaries and have a supporting and nutrient 
function; the cells of the oligodendroglia take part in myelin formation; the 
microglia cells are part of the reticuloendothelial system and hence are migratory 
and phagocytic. 

Inasmuch as the neuron is the unit of neuronal function and the synapse is 
the point of junction of neurons, if one understands the anatomy and physiology 
of chains of neurons and knows not only the minute details of physiology but 
the gross function of all neuronal complexes, as these function in groups for the 
benefit of the organism, one understands the entire groundwork of sensation, motor 
function, emotions, thoughts, conditioned reflexes, knowledge, wisdom and psy- 
chology. All functions of the central and peripheral nervous system as well as 
of the vegetative nervous system depend on the function of the neurons, on the 
conduction of impulses. We must, therefore, know something of the nature of 
the nerve impulse. 

There has been a tremendous amount of study devoted to the question whether 
the nerve impulse is primarily electrical or chemical. It has been settled that the 

Vol. VI. 1245 



REFLEX ARC 3 

synaptic transmission is chemical, but all the details of the nerve impulse itself 
are not entirely understood. The action current in a nerve is a wave of negativity, 
and activity is associated with a flow of ions. The nerve impulse propagates itself 
along the nerve fiber. Conduction is accompanied with a consumption of oxygen 
and liberation of carbon dioxide and heat. The axon is a protoplasmic core sur- 
rounded by a membrane which lies in tissue fluid. The membrane is relatively 
resistant to passage of ions in and about the membrane, and there are ions on both 
sides of it. If an impulse travels, it is a maximum one; nerve fibers, like muscle 
fibers, obey the " all or none " law. The impulse is propagated as an active chem- 
ical phenomenon. Adrian- says: " The nerve impulse is a little patch of surface 
leakage spreading along the fiber and being sealed up again as soon as it is formed." 
A breakdown of phosphocreatins and perhaps, of phospholipins occurs. The 
muscles receive a volley of impulses at the rate of 50 to 90 per second from each 
neuron. Because of polarization at the synapse, impulses normally travel in only 
one direction, from the cell body down the axon. The speed of conduction along 
the axon varies according to the size of the axon; speeds of 80 to 120 meters per 
second are common in the human subject. 

At the synaptic junction, and perhaps all along the axon, acetylcholine is 
liberated as the nerve impulse passes. This substance has a powerful and rapid 
stimulating action on the end plate region of the muscle and is rapidly hydrolyzed 
by an enzyme, cholinesterase, concentrated at or near the end plates. The rapidity 
and chemical specificity of the acetylcholine effect suggest that acetylcholine pro- 
duces its polarizing action by combining with specific chemical receptors on the 
surface of the muscle fiber. Adenosinetriphosphate is the specific chemical sub- 
stance involved in the generation of muscular energy. 

The neuronal cell bodies or perikaryons form the bulk of the cortex of the 
cerebrum and cerebellum, the gray matter of the corpus striatum, the thalamus, 
all nuclei, including the nuclei of the cranial nerves, the gray matter of the spinal 
cord and the ganglia of the vegetative nervous system. Myelinated processes 
of the ganglion cells form the bulk of the white matter of the brain and spinal 
cord and the sheathed neurons of the peripheral nerves. Inasmuch as a single 
neuron probably never acts alone, the reflex arc, consisting of two or more neurons, 
becomes the functional unit of neuronal physiology. 

Reflex Arc 

The simplest reflex arc, such as a segmental reflex arc of the spinal cord, con- 
sists of a receptor, a sensory (bipolar) neuron, a synapse and the motor nerve to 
the elector (Fig. i). It is probable that an intercalated neuron, a third neuron, 
is present always even in the simplest reflex arc. The motor neuron with its 

Vol. VI. 1245 



4 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

termination in the muscle or gland commonly is called a motoneuron. Receptors 
are of various types each with a special function. Naked nerve endings serve for 
sensitivity to pain, Meissner's corpuscles for touch, Pacinian corpuscles for deep 
pressure, Krause's end bulbs for cold, Ruffini's end organs for warmth and so 
forth. The retina serves for sensitivity to light, the organ of Corti for sound, 
tactile hairs in the bulbs of the semicircular canals for movement of the endolymph, 




SKIN' 

Fig. I. Diagram of the simplest spinal reflex arc of three neurons. Skin is illustrated as 
the source of the afferent impulse; the impulse may originate in muscle or tendon. (Modified 
from Purves Stewart, Oxford Medicine, Chapt. I, Vol. vi, Oxford Univ. Press, New York, 
1Q26.) 



olfactory epithelium for smell and taste buds for taste. If any stimulus is suffi- 
ciently intense, pain results. 

A distinction should be made between perception of pain and the attitude of 
the individual toward it, that is to say the emotional reaction. One can be trained 
to a certain extent to have emotional reaction to pain; those who suffer a great 
deal over a long period of time become inured to it, although there is no evidence 
that the pain receptors are in any way altered. The Amerindian is proverbially 
stoic; pampered persons are plaintive. Besides the element of training there is a 
constitutional element; members of certain families have no emotional reaction 
to pain, although they perceive it. In one family under the observation of the 
writer two girls could be operated upon without anesthetic, while a brother was 
so exquisitely sensitive that a casual contact with another person in passing on 

Vol. VI. 1245 



TYPES OF SPINAL REFLEXES 5 

the street made him wince, and often weep, with pain. Two other families of 
persons insensitive to pain have been encountered. 

As stated above, synapses are polarized ; impulses normally travel in only one 
direction, from the dendrite to the cell body and from the body through the axon. 
By artificial stimulation of a peripheral nerve the nerve impulse may be made to 
travel in either direction but not across a synapse. Impulses can be summated 
in a reflex center but not in a fiber; thus a subliminal stimulus, if repeated, may 
accumulate at the cell body until the threshold is crossed. Variations in strength 
of stimuli cause a corresponding gradation in reflex response, not that impulses 
vary in strength in a given fiber, but that more fibers may take part, if the stimulus 
is stronger. Furthermore, an ineffectual stimulus causes a central excitatory state 
in the ganglion cell in such a manner that subsequent stimuli may rise above the 
threshold value. If the same stimulus is merely continued, recruitment may cause 
activity in more motoneurons and thus give rise to reflex action. 

The simplest reflex arc, as stated, involves two neurons. It is, however, rather 
the exception than the rule to have a two-neuron reflex. As stated, even the 
simplest spinal reflexes generally involve an intercalated neuron. The great 
majority of reflexes involve chains of neurons. 

The great master of neurophysiology, Sherrington^, as recorded in his book 
The Integrative Action of the Nervous System, showed in experimental work on 
dogs that the spinal cord, separated from the higher levels, was capable of a re- 
markable degree of integration. The general law was established that an irritation 
produces a movement, not a muscular contraction. Now. as it is well known that 
nearly all muscles in the body are supplied from three successive segments of the 
spinal cord, it must be clear that an impulse entering through a single segment 
spreads up and down the cord to stimulate at the very least anterior horn cells in 
three segments. However, inasmuch as antagonistic muscles in any movement 
must be inhibited to allow orderly contractions of the protagonists, there must be 
present in the spinal cord a coordination mechanism, an integration pattern, to 
cause simultaneous stimulation in one group of muscles and inhibition in another. 
Sherrington showed that there are segmental and intersegmental spinal reflexes. 

Examination of the spinal cord shows that there are short ground bundles of 
White fibers immediately applied to the gray matter. These bundles serve for 
coordination within the spinal cord. The white matter, as seen on cross section, 
evidently is nearly as voluminous for these ground bundles as for all of the long 
fiber tracts. 

Types of Spinal Reflexes 

Flexor Reflex. — This spinal reflex is the most primitive of all. It consists 
of a flexion withdrawal of a limb from a noxious stimulus. The reflex is more 
Vol. VI. 1245 



6 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

violent from an irritation of the skin than it is from stimulation of deep sensory 
nerves. It represents a defense mechanism against nociceptor stimuli. Literally 
thousands of neurons must take part in such a coordinated movement which flexes 
hip, knee, ankle and sometimes, digits. The ganglion cells of the cord " seem 
to think '", inasmuch as a useful purpose is served by the reflex. However, since 
the reflex centers have no choice, the reflexes are clearly inherited functional pat- 
terns acquired by milleniums of usage. 

The clinical importance of the flexor reflex is widespread. It is the basic cause 
of doubling-up in acute abdominal disease, in " sciatica " and, as Fulton* points 
out, probably in arthritis. When the clinician elicits a Babinski sign, he must 
always guard against accepting the general flexion movement as a positive sign. 
The examiner's stimulus must be graded to fit the sensitivity of the sole of the foot, 
and the mass flexion is wisely avoided or prevented by the examiner during the test. 

Stretch Reflex. — Sherrington discovered the extension reflexes in decere- 
brate dogs. They depend on the stretch reflex, the receptor end organ of which 
is the muscle spindle found in the red muscle fibers. This reflex acts selec- 
tively upon antigravity muscles and is the basic reflex for posture. Simply stated, 
the stretch reflex is elicited in an appropriate muscle simply by stretching it very 
slightly; the muscle then contracts and remains in tonic contraction for a long 
time; fatigue hardly occurs. 

Through the work of Denny-Brown, now of Harvard University, and many 
investigators prominent among which are the physiologists of Yale University it 
has become the modern concept that the red muscle fibers occurring in various 
muscles are the ones serving chiefly in maintenance of posture, and that the 
muscles with such fibers are the ones which become rigid in reflex standing. They 
particularly resist the effects of gravity. By the universal law of reciprocal in- 
nervation, by which through spinal coordination the antagonists are inhibited 
when certain muscles are stimulated, the flexors are coordinated with the exten- 
sors in the extensor reflex. Decerebrate rigidity is reflex standing. 

In the intact animal and in the human subject it is clear that reflex posture is 
modified by higher centers, particularly the cerebral cortex. There is a certain 
correlation possible, which the writer has not seen in the literature but which 
seems suggestive, that normal standing and walking are normally relatively free* 
from cortical control. The generally accepted basic facts, which do not seem to 
require proof and from which a corollary can be drawn, are as follows: 

1. A normal person stands and walks with an habitual pattern not requiring 
attention unless external factors bring about necessity for change. 

2. Habitual acts, which no longer require attention, are integrated in the basal 
ganglia, particularly the putamen and globus pallidus with their lower connections 
— the red nucleus, corpus subthalamicum and reticular formation. 

Vol. VI. 1245 



FINAL COMMON PATHWAY 7 

3. In paralysis agitans, in which the disease process affects the projection fiber 
system of the globus pallidas, reflex standing and walking are particularly dis- 
turbed. The disease produces festination and abnormal postures with weakening 
of the antigravity muscles. The normal postures and normal walking can be car- 
ried out, if the patient uses his cortex to think out what needs to be done. How- 
ever, since normal walking usually is not thought out, the walking, which thus is 
cortically managed, is a caricature of the normal. 

Intersegmental Reflexes. — The intersegmental reflexes have already been 
mentioned. By virtue of these the well-known scratch reflex of the decerebrate 
dog or frog enables the animal to scratch the appropriate spot with the hind foot, 
when the skin of the trunk is irritated. There are also positive and negative sup- 
porting reactions in the dog whose spinal cord is isolated from the brain. These 
are illustrated by extension of the limbs of the side toward which the standing 
dog is gently pushed, and relaxation of the opposite limbs. This reflex serves an 
obvious purpose and makes cerebral guidance of posture unnecessary under such 
circumstances in the normal animal. 

There are also visceral segmental reflexes. These include engorgement of the 
genitalia with assumption of the characteristic copulation posture when the 
perineum is stimulated. The bladder and rectum will empty reflexly when a cer- 
tain degree of distension of the viscera has been attained. A mass reflex is evoked 
also by appropriate stimuli ; this results from a diffusion of the impulses in the cord 
and may cause in addition to the reactions just described also sweating and rise 
of blood pressure. These reactions are seen in a modified degree in man after re- 
covery from spinal shock in cases of transection of the cord. 

Final Common Pathway 

The anterior horn cells of the spinal cord, the lower motor neurons, are not 
mere passive ganglion cells subject to reflex action. They are small coordinating 
centers themselves. They receive all of the reflex stimuli described above for final 
transmission to the effectors, but they receive also a tremendous flux of impulses 
from higher centers in the intact animal or human being. They receive impulse 
from (Fig. 2); (i) the cortico-spinal tracts (pyramidal tract and prepyramidal 
pathways), (2) the rubrospinal tract, (3) the reticulospinal tract, (4) the tecto- 
spinal tract, (5) the vestibulospinal tract, (6) the ground bundles from other levels 
of the spinal cord, (7) proprioceptive and exteroceptive impulses reflexly. 

The anterior horn cells are played upon by all these sources of stimuli and must 
accept, reject and modify these impulses and pass on to their axons the algebraic 
sum of all of them in the best interests of the organism. It is for this reason that 
Sherrington called the lower motor neuron the final common pathway. 
Vol. VI. 1245 



8 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 




Fig. 2. Diagram to show the sources from which impulses converge 
on the anterior cornual cell. Py, pyramidal tract; T-S, tectospinal tract; 
R-S, rubrospinal tract; D-R, dentatorubral tract; V-S, vestibulospinal 
tract. The cell out of place on the border of the anterior horn repre- 
sents a lateral cornual cell of the sympathetic system. (Redrawn from 
Purves Stewart, Oxford Medicine, Chapt. I, Vol. vi, Oxford Univ. Press, 
New York, 1926.) 



Vol. VI. 1245 



LOWER SENSORY NEURON 9 

Lesions of the Lower Motor Neuron 

The " lower motor neuron lesion " is a concept of great value to clinical neu- 
rology. Inasmuch as the cell body of the neuron in the anterior horn of the spinal 
cord or in the brain stem for the homologous cranial nerves is the nutrient center 
for the axon, degeneration of the cell body will cause degeneration of the entire 
axon, and section of the axon will cause degeneration of the entire peripheral end. 
Furthermore, the lower motor neuron is the trophic mechanism necessary for 
preservation of the muscle fibers supplied by it. Incidentally, the synaptic 
boutons of other neurons ending at the anterior horn cell will degenerate, if the 
cell body is damaged. 

When a motor nerve is cut, the nerve beyond the section will undergo degenera- 
tion simultaneously all along its course. The myelin sheath will disintegrate into 
droplets and will disappear gradually, as the products are absorbed by scavenger 
cells. Each cut axon also will degenerate centrally to the first node of Ranvier. 
The cells of the neurolemma will proliferate. This form of degeneration is known 
as Wallerian degeneration, named for Waller, who first described it. As regenera- 
tion takes place, new fibers are generated at the rate of 3^ to 4 mm. a day accord- 
ing to whether the channels are well apposed or not and according to other 
favorable or unfavorable circumstances. 

The symptoms of degeneration of a set of lower motor neurons in the spinal 
cord, assuming a considerable number to render the symptoms clinically identi- 
fiable as in chronic anterior poliomyelitis, are as follows; (r) flaccidity of muscles, 
(2) loss of reilexes, (3) fibrillation or fasciculation in the affected muscle fibrillae 
or fasciculi, (4) degeneration of the motor end plates in the muscles, (5) atrophy 
of the affected muscles, (6) reaction of degeneration (R.D.) and increase in the 
chronaxia, (7) contracture in antagonists of the affected muscles. 

As nearly every voluntary muscle in the body is supplied by three successive 
motor roots, the section of a single root will cause atrophy and fasciculation only 
in the muscle fascicles supplied by that root. However, not all fasciculation is of 
central origin. Damage to the neuromuscular end plates will cause it also. Hence, 
it is correct to state that damage to any portion of the lower motor neuron may 
cause fasciculation — even excessive fatigue or interference with the blood supply 
of a muscle. 

Lower Sensory Neuron 

The lower sensory neuron has its cell body in the posterior root ganglion. Its 

peripheral fiber begins in a receptor in the skin, tendon or muscle. The central 

fiber ends in the gray matter of the spinal cord, posterior horn region or in the 

nuclei gracilis and cuneatus. The distribution of the cutaneous fibers of a nerve 

Vol. VI. 1245 



10 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 



are quite different from the distribution of the radicular fibers because each nerve, 
especially in the limb region, passes through a plexus and sends its component 
fibers to the spinal cord through several roots. The section of Oxford Loose Leaf 
Medicine on the peripheral nerves must be consulted for the cutaneous distribu- 





FiG. 3. Photograph of Henry Head's dermatomes based on lesions of herpes zoster, 
Brain, xxiii, 1900. 

tion of the various nerves; here will be explained the manner of cutaneous dis- 
tribution of the fibers in roots. 

The first great principle is that the dermatomes overlap. Head worked 
out a most intricate distribution for each root based on the cutaneous lesions in 
cases of herpes zoster (Figs 3, 4a, 4b and 5), in which the posterior root ganglia 
are the seat of infection. The enormous advances of neurosurgery have made 
available innumerable cases of section of individual roots, done for various rea- 

VoL. VL 1245 



LOWER SENSORY NEURON 



II 



sons. It has been found that the section of a single root gives a variable but re- 
markably limited loss of sensory perception, best tested by sensitivity to pin prick. 
This method gives for each root only the area of skin supplied exclusively by that 
root, but as the adjoining roots supply overlapping areas, the actual extent of sup- 



Radiculor Distribution of Cutaneous Areas Radicular Distribution of Cutaneous A 



reas 




Fig. 4. Radicular distribution of cutaneous areas simplified for practical diagnostic pur- 
poses. (From Nielsen, Textbook of Clinical Neurology, Hoeber, New York, 1941.) 

ply of a root is not thus determined. If, on the other hand, the roots above and be- 
low a given root are sectioned, the area of retained sensibility is much larger because 
the overlap of that dermatome on the others is included. The chart shown is a 
working system to which, while no specific case may absolutely conform, any case 
will conform sufficiently to be of clinical application. 



Vol. VI. 1245 



12 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

Distribution of Nerves to the Head 



Trigeminal Net 
First 

(ophthalmic^ 
division. 



Second 
(maxillary) 
division.. — - 

Third ------ 

(nnandibular) 
division. 




Branches 
frorn third 
cervical roots. 



Fig. 5. Trigeminal and radicular distribution to head and neck. (From Nielsen, Text- 
book of Clinical Neurology, Hoeber, New York, 1941.) 



Gross Anatomy of the Spinal Cord 

The spinal cord extends from the medulla oblongata to its termination between 
the first and second lumbar vertebrae, from which point the filum terminale ex- 
tends to the tip of the coccyx. It lies ensheathed in pia mater and arachnoid with 
a relatively large intermediary subarachnoid space in which the cerebrospinal 
fluid is found. Outside the arachnoid is the dura mater. Between the latter and 
the spinal column is a pad of epidural fat. The spinal cord hangs relatively free 
in the subarachnoid space, reaching, as stated, in the adult, to a point between the 
first and second lumbar vertebrae. Below this point the cauda equina is found; in 
that area spinal punctures can be done without trauma to the cord. 

The spinal cord consists of a core of roughly H shaped gray matter with a tiny 
central canal, surrounding all of which are tracts of white matter (Fig. 6). The 
cross-sectional appearance is only crudely H formed, and it varies greatly at vari- 
VoL. VI. 1245 




u 



w 



rt 



o 



14 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

ous levels. As the large bodies of motor neurons lie chiefly in the anterior horns, 
these horns are large at the levels at which any large nerves or plexuses are to be 
formed, at the cervical and lumbar enlargements. The increased size of the gray 
matter causes a general swelling in the cord at those levels. The blood supply is 
shown in Fig. 7. 



POSTERIOR SPIK)Al. aRTER.Y 




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ANTR. RADICULAR 
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Fig. 7. Blood supply of spinal cord (schematic). 



The nerve roots, which form the connections between the spinal cord and the 
peripheral nerves, are two in number at each segment, one anterior motor root 
and one posterior sensory root. The cell body of the anterior root lies in the an- 
terior or ventral horn of the gray matter ; the cell bodies of the posterior root lie in 
the ganglia, which occur on each just central to the point of junction of the two 
roots to form a nerve. After the two roots have united, a single nerve is formed, 
which may then continue as such or may enter a plexus for more efficient distribu- 
tion of the nerve fibers according to requirements of the limb musculature. 

Emerging from the spinal cord with the anterior root is a sympathetic neuron 
with cell body in the lateral horn of the spinal cord. It follows the anterior horn 
to a point outside the spinal foramen and then makes its exit to the sympathetic 

Vol. VI. 1245 



GROSS ANATOMY OF THE SPINAL CORD 15 

chain through the white ramus communicans. If it is destined to return, it re- 
enters through the gray ramus to be distributed with the spinal nerves. The gray 
matter contains the bodies of the neurons, whose axons are to form the peripheral 
motor nerves. It also contains intercalated neurons, which serve to form multiple 
connections of one axon of a fiber tract (of the white matter) or of one sensory 
fiber entering through the posterior horn with many motor neurons. In this way 
the gray matter acts as a great coordinating center for segmental and inter- 
segmental reflexes as already outlined. 

The white matter consists of fiber tracts. Those which immediately adjoin the 
gray matter are short or long ground bundles of association tracts uniting neurons 
of various segments for coordinated action. Long fiber tracts, conveying impulses 
down from the brain or up to it, lie slightly farther from the gray matter. Between 
the posterior horns are the two tracts of Goll and Burdach, gracilis and cuneatus, 
which convey proprioceptive impulses upward to the nuclei of the same names at 
the lower border of the medulla. Up to the level of those nuclei the fibers are 
uncrossed, i.e. they convey impulses from the same side of the body. The fibers 
from the lower part of the body are placed close to the midline septum and, as 
the fibers enter from higher levels, these take places more laterally. In the upper 
part of the cord the fibers from the upper limbs thus are placed nearer the posterior 
horn of the gray matter. These fibers convey impulses conveying perception of 
position and vibration and some impulses of tactile perception. It is not the same 
fibers which convey each form of sensation but different ones; all are variously 
susceptible to disease and toxins in such a manner that clinically any form of 
perception may be lost without the other. 

The clinical application of these facts is that tactile sensation as well as sensa- 
tions of vibration and position are uncrossed ; a unilateral lesion of the cord causes 
loss of such perception below the lesion on the same side. 

The spinothalamic tracts are organized quite differently. The tracts are placed 
laterally just anterior to the midline as seen on cross section. Their fibers are re- 
ceived from the opposite posterior roots after crossing in the gray commissure. The 
fibers are located in a laminated system, those from the lowest levels being antero- 
lateral; the higher levels of the sensation (from the upper limbs) are located 
postero-medially. This fact is of great clinical importance because chordotomy 
for relief of intractable pain can be done in the latero-anterior aspect for relief of 
pain in the lower limbs without a deep incision, which might impinge upon the 
pyramidal tract. 

The corticospinal tract, pyramidal tract, which arises in the precentral gyrus 
of the opposite frontal lobe forms this tract after its passage down the internal 
capsule, cerebral peduncles, mesencephalon, pons and medulla (Fig. 8). The 
crossing occurs in the lower part of the medulla, and the tracts take their places 

Vol. VI. 1245 



i6 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 




Fig. 8. Untouched photograph of author's section through the pyramidal 
tracts of human brain. The tract can be traced from the corte.x, through the in- 
ternal capsule (between the thalami medially and the lenticular nuclei laterally), 
through the cerebral peduncles between the internal capsule and the pons, through 
the pons and medulla oblongata. In the medulla the decussation of the pyramidal 
tracts can be seen. 
Vol. VI. 1245 



" CENTERS " IN THE SPINAL CORD 17 

just behind the midline as seen on a cross section. They lie between the ground 
bundles mesially and the posterior spinocerebellar tracts laterally. 

The physiology of this tract has been considered understood for many decades; 
we are just discovering that our supposed knowledge was largely false. It has 
been conventional to state that they were the motor tracts for voluntary motion, 
that they conveyed the chief impulses required for voluntary activation of the 
anterior horn cells and that they suppressed reflex activity of those cells. 

However, through the brilliant experimental operations on chimpanzees by 
Rothman, Marshall and especially by Sarah Tower^ and Marion Hines" and by 
occasional natural experiments in the human subject it has been found that sec- 
tion of the the pyramidal tracts causes weakness rather than paralysis and that 
those tracts stimulate rather than inhibit the activity of the lower motor neurons. 
Instead of increasing the deep reflexes, section of the pyramidal tract diminishes 
them. These revolutionary findings, now undeniable, compel us to revise our 
concepts. 

The modern concept is that the extrapyramidal tracts (frontal extrapyramidal, 
rubrospinal, reticulospinal, tectospinal, vestibulospinal) and the ground bundles 
are capable of considerable voluntary action. Moreover, it is damage to elements 
of the extrapyramidal fibers which causes an increase in the deep reflexes and 
inhibition of the superficial ones in cases of upper motor neuron lesions. It is 
damage to extrapyramidal fibers which causes spasticity; paralysis of the pyra- 
midal tract causes flaccidity which, however, is less marked than the flaccidity due 
to a lower motor neuron lesion. The cause of the Babinski sign is still considered, 
as heretofore, a lesion of the pyramidal tract. 

The symptoms of upper motor neuron disease, for practical purposes, are still 
as they have conventionally been ; ( i ) increase of the deep reflexes, ( 2 ) diminution 
of the superficial reflexes, (3) spasticity with contractures, (4) absence of atrophy 
except such as results from disuse, (5) appearance of the Babinski sign or its 
equivalents. 

One must merely keep in mind that the " upper motor neuron " is not merely 
the neuron of the pyramidal tract. 

" Centers " in the Spinal Cord 

A " center ", in the sense in which the term is used in this article, is not a 
compact group of cells anatomically delimited but a group of cells closely grouped 
or diffusely associated for the performance of a given function and whose destruc- 
tion is recognizable by symptoms. In this sense there are centers in the lumbo- 
sacral spinal cord for control of bladder and rectal functions. These centers after 
infancy are normally under voluntary control to a certain extent, but if the viscera 

Vol. VI. 1245 



i8 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

in question are overdistended, or if they are separated (by organic lesions) from 
higher control, they escape such control and act to a certain extent automatically. 
In the same sense there are diffuse " centers " or mechanisms, associated with fiber 
tracts, for coordinated movements of flexion or extension of the lower limbs. In 
certain ecstatic states such movements come into play. 

The clinical importance of such mechanisms, some of which have been de- 
scribed already, is their display in cases of section of the spinal cord. If the spinal 
cord of a human being is severed suddenly as by a bullet or a knife, there super- 
venes immediately a state of " spinal shock " due partly to the suddenness of iso- 
lation and partly to vasomotor paralysis. If the section is acute, but less sudden, 
as in cases of transverse myelitis, the symptoms of spinal shock are present but 
somewhat less marked. In general the higher the level of the lesion, the more severe 
the symptoms. 

In such cases the reflexes all disappear, deep and superficial, below the lesion. 
The bladder and rectum empty themselves periodically, involuntarily and without 
the patient's knowledge. There is a strong tendency for extensive trophic lesions 
of the skin to develop, and only meticulous care will prevent ascending urinary 
infection and decubitus ulcers. 

A lesion of the third or fourth cervical segment will destroy the center for 
diaphragmatic control and hence will cause acute paralysis of the diaphragm. Also 
it will cause priapism, as a rule, in the male. Hyperthermia sometimes results 
from a high cervical lesion, although the mechanism is not understood. 

At the first and second cervical segments is located another center, an organ- 
ization of cells made up of intercalated neurons which function in tonic neck 
reflexes. The function of this center will be clarified, when the medulla oblongata 
is discussed. 

In cases of slowly developed lesion of the cord, such as caused by a neoplasm, 
the symptoms can be studied in greater detail. At first there is weakness of the 
lower limbs; this is followed soon by spasticity. Then the bladder sphincter is 
difficult to relax, and distension with overflow appears. By that time obstipation 
is evident. The Babinski sign or its equivalent develops, and we have a case of 
spasticity in extension; the lower limbs are difficult to flex; next flexor spasms 
appear followed by flexion contractures of the lower limbs and complete loss of 
control of the sphincters. We now have spasticity in flexion, a sign that the spinal 
cord is essentially severed. 

In cases of severance of one lateral half of the spinal cord there is loss of tactile 
and proprioceptive sensation with loss of voluntary motion on the same side below 
the lesion and loss of temperature and pain perception of the opposite side. This 
is known as a Brown-Sequard syndrome. In slowly oncoming lesions, as from 
compression by a unilateral neoplasm, all of the signs of spasticity of the ipsilateral 

Vol. VI. 1245 



MEDULLA OBLONGATA 19 

limb may be seen before the paralysis develops. In such cases the sphincters re- 
main under voluntary control because the centers in the lumbosacral cord are 
innervated bilaterally. 

Medulla Oblongata 

While the medulla oblongata is traversed by important ascending and de- 
scending tracts, which do not have synapses there, it is, besides, the seat of centers 
of vital importance to the organism. In the lower portion is found the " respira- 
tory center ". The delineation of the center is not exact in man, although in the 
cat an inspiratory and an expiratory center have been demonstrated. In man the 
respiratory center is located " at the calamus scriptorius ". 

Anatomically it is a matter of highest importance that the cells constituting 
this center are located on both sides of the midline, and that the two halves are 
united so intimately with association fibers that destruction of one pyramidal 
tract above the medulla does not deprive the individual of his usual voluntary 
control over both sides. Another anatomical fact of vital importance is that the 
cells are not lower motor neuron cells; they belong to the intercalated system and 
constitute a coordinating mechanism for the anterior horn cells which function in 
respiration. 

The respiratory center may be used as a paradigm for supranuclear coordinat- 
ing mechanisms in general, of which there are many. There is one in the region 
of the mesencephalon just anterior to the superior colliculi, whose function it is to 
coordinate extraocular muscle nuclei for the function of upward and downward 
gaze and one for convergence of the eyes. There are others in the lumbosacral 
cord for coordination of sphincteric control. Still another governs action of the- 
abdominal and cremasteric muscles. In the pons is found another for coordina- 
tion of the upper facial muscles. In short, there are supranuclear coordinating 
mechanisms for all truncal structures which must function only in pairs. 

The respiratory center is the most highly developed of all these mechanisms 
and has a separate humeral control. Even when it is deprived of all pyramidal 
innervation, as in cases of decerebrate rigidity or in severe cases of amyotropic 
lateral sclerosis, the respiratory center continues to function in response to the 
COo tension of the blood. It also responds to reflex stimuli, to function in reflex 
coughing and sneezing. Thus in cases of pseudobulbar palsy, when the patient 
has lost voluntary ability to hold his breath, to cough, to sigh or to sneeze, the 
center will enable him to do all those things reflexly. He holds his breath to 
evacuate his bowels: he hiccoughs, if the diaphragm is irritated; he coughs, if 
particles get into his larynx; he sneezes, if his nose is tickled. In cases of bulbar 
palsy, in which the nuclei of the hypoglossal nerves and other nuclei in the bulb 

Vol. VI. 1245 



20 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

degenerate, the respiratory center does not undergo degeneration, because it 
belongs, as stated, to the intercalated, or internuncial, neuronal system. 

Of extreme importance to an understanding of equilibrium in general, specifi- 
cally to equilibrium of the head and eyes, and in relation to bodily posture and 
eyes, are the vestibular nuclei. These nuclei are located laterally in the medulla 




Fig. 9. Horizontal section of the cerebellum to show the actual relationship of the fastigial, 
globose and embolliform nuclei. (Section made by Clemson Marsh.) 

and extend dorsally into the walls of the fourth ventricle. The labyrinth consists 
of two physiologically different mechanisms, the static utricle and saccule and the 
kinetic semicircular canals. 

The vestibular nuclei receive their impulses from the periphery by way of the 
vestibular nerves from the labyrinths. Scarpa's ganglion in the course of the 
nerve is homologous with a posterior spinal root ganglion. The vestibular nuclei 
also have important connections with the flocculonodular lobe of the cerebellum 

Vol. VI. 1245 



MEDULLA OBLONGATA 21 

and with the fastigial nuclei in the roof of the fourth ventricle (Fig. 9). These 
nuclei are part of the paleocerebellar structure as is the flocculonodular lobe. 
The vestibular nuclei have further important connections with the posterior longi- 
tudinal bundle, median longitudinal fasciculus, which is the most important asso- 
ciation tract between the nuclei of nerves supplying the extraocular muscles. 
The vestibular nuclei, especially Deiters' nucleus, give rise to the vestibulospinal 
tract whereby the trunk and limbs respond to vestibular reaction. Finally, there 
is a direct connection with the neck muscles whereby movements of the head 
alone may respond to vestibular impulses. 

Tonic labyrinthine reflexes have their greatest influence through the utricular 
stimuli affecting the tone of the entire musculature. Even when tonic neck re- 
flexes are excluded (by section of all the uppermost afferent roots or by encasing 
the neck in a plaster cast), an extensive influence on the antigravity muscles is 
found. The greatest extension effect is obtained when the animal is supine with 
snout at 45 degrees above the horizontal. Minimal effect is obtained at a point 
after rotation about a transverse axis, when the snout is 45 degrees below the 
horizontal level. 

Through connections of the vestibular nuclei with the centers for tonic neck 
reflexes these latter are influenced by the vestibular reactions. There are also 
labyrinthine righting reflexes, by which the head is held as much as possible in its 
proper relation to the level of the earth, but the righting reflexes all operate through 
the midbrain. The pathway is from the vestibular nuclei to the cerebellum, thence 
by way of the superior cerebellar peduncles to the red nuclei and downward through 
various mesencephalic-spinal tracts. Labyrinthine-ocular reflexes function 
through the posterior longitudinal bundles. 

Nystagmus, while usually considered pathological, is useful normally to per- 
mit ocular fixation on an object during head movements, for example, to permit 
a dog to keep its eyes on a rabbit, while the positions of the head and body are 
constantly changing, or to permit watching of passing game without necessitating 
movement of the head. The mechanism fatigues with long use, as every traveller 
has experienced in watching objects from a train. 

Destruction of one labyrinth causes skew deviation of the eyes, the ipsilateral 
eye being directed downward, the contralateral, upward. Destruction of the 
vestibulo-cerebellar connections may produce a similar syndrome. 

The vestibulo-spinal tract is essential to the tonic neck reflexes of Magnus and 
de Kleyn (see Fulton*) as seen in decerebrate rigidity. When fully developed, 
these reflexes are as follows : 

Rotation of the head to the right causes the right limbs to go into extensor 
rigidity, while the left limbs flex. Flexion of the head to the side produces the 
same effect but usually to a less marked degree. Rotation to the opposite side 

Vol. VI. 1245 



22 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

produces the opposite effect. Flexion of the head forward causes the upper limbs 
to flex, the lower to extend. Pressure on the vertebra prominens causes relaxa- 
tion of all limbs. In the human subject these reflexes are rarely completely de- 
veloped, but, if the clinician will study his cases carefully, he can often detect at 
least a lessening tone of the limbs toward which the occiput is turned and an 
increase in the others. This fact is of considerable value in diagnosis of compres- 
sion of the brain stem or of hemorrhage into it. 

Also located in the medulla are the nuclei of the vagus nerves with their im- 
portant influence on the cardiac rate and upon blood pressure. Compression of the 
medulla causes first slowing of the pulse rate to a certain point. The cardioin- 
hibitory mechanism finally fails, and the heart races to an uncountable rate until 
the heart ceases entirely. The respiratory mechanism does not behave in the same 
way ; respiration becomes slower and slower until it ceases. 

In the lower portion of the medulla are located the nuclei gracilis and cuneatus, 
the first synaptic site for the proprioceptor fibers from the posterior root ganglia. 
Leaving the nuclei the arcuate fibers descend (go forward) and cross in the sensory 
decussation ( above the motor), sending their fibers to the lateral nucleus of the 
(contralateral) thalamus. 

Pons 

The pons or bridge is essentially a mass of gray matter made up of nuclei, 
whose axons pass into the cerebellar hemisphere, and of smaller nuclei constituting 
the recticular formation of the pontine tegmentum (Fig. lo). This mass of gray 
matter is traversed by the fibers of the pyramidal tract, the rubrospinal tract, the 
tectospinal tract, the central tegmental fasciculus and the fibers of the retriculo- 
spinal system. Terminating in it are the fibers of the frontopontine and tem- 
poropontine tracts. All tracts ascending from the spinal cord to higher centers 
traverse the pons. The posterior longitudinal bundle and the corpus trapezoides 
are structures of importance for coordination of eye movements and for hearing 
respectively. 

Located close to the nuclei of the sixth cranial nerves is a center of intercalated 
neurons for coordination of lateral gaze. The effect of a lesion in this center is to 
prevent movements to one side with a resultant fixation of the eyes away from 
the lesion. 

Cerebellum 

Through the work of LarselF the functional organization of the cerebellum 
seems finally to have been elaborated to the satisfaction alike of zoologists, embry- 
ologists, anatomists, physiologists and clinicians. The cerebellum develops as an 
outgrowth from the medulla oblongata, especially from the vestibular group of 

Vol. VI. 1245 



CEREBELLUM 



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Vol. VI. 1245 



24 .\NATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

nuclei. It is primarily concerned with elaboration of vestibular mechanisms and 
hence of equilibrium. The paleocerebellum still is concerned with those functions, 
while the relatively enormous hemispheres, which constitute the neocerebellum. are 
concerned with coordination of limb movements. The two sets of function may 
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NEOCEREBELLUM 

Fig. II. Scheme of the cerebellum according to Larsell and Dow. (Redrawn from Ful- 
ton, Physiology of the Nervous System. O.xford Univ. Press, New York, 1943.) 



The paleocerebellum consists of the anteriorly placed lobules, the lingula, 
centralis and culmen and the posteriorly placed pyramis, uvula and flocculonodular 
lobe (Fig. II.) Of these the lingula, uvula and nodulus have vestibular connec- 
tions, the others, spinal. The vestibular nuclei also have important connections 
with the fastigial, globose and emboliform nuclei. 

Vol. VI. 1245 



CEREBELLUM 25 

From extirpation experiments it has become clear that the removal of the 
flocculonodular lobe, and not of any other part of the cerebellum, causes isolated 
disturbances of equilibrium, i.e. disturbances without volitional tremor or altera- 
tion of reflexes. This conception is entirely substantiated by clinical experience 
in that the common medulloblastoma of childhood, which arises from that lobe, 
gives precisely such symptoms. 

Furthermore, it is known that after destruction of the labyrinths extirpation of 
the flocculonodular lobe does not cause additional symptoms. The dentate nuclei 
and the main body of the hemispheres are constituents of the neocerebellum. The 
afferent fibers of the dentate nucleus are from the Purkinje cells of the lobes; the 
efferent fibers pass upward through the superior cerebellar peduncles, some to, 
others through, the red nucleus. Those which terminate there end in part in the 
magnocellular, in part in the parvocellular nucleus. Those which pass through 
end in the lateral part of the lateral nucleus of the thalamus. After another relay 
fibers terminate in the frontal cortex, areas 4 and 6 of Brodmann. According to 
Fulton* this projection contributes little to the influence of the rubrospinal tract, 
as its chief termination is in the parvocellular nucleus and thence to the cerebral 
cortex. However, I believe with Spatz that the central tegmental fasciculus, which 
arises from the red nucleus and descends into and through the entire tegmental 
reticular formation and into as well as past the inferior olive, by relays reaches the 
ground bundles of the spinal cord and has a tremendous influence on posture in 
a completely unconscious manner. 

A point of prime importance in all cerebellar connections is that, because of 
double decussation of all connections, the cerebellar influence is ipsilateral to the 
cerebellar lobe. Stimulation of the anterior paleocerebellum causes inhibition of 
ipsilateral antigravity muscles. The neck and each limb have individual repre- 
sentation. 

In man the neocerebellar structure is far larger than the paleocerebellar, and 
hence it must be considered important functionally. It is related to the limbs, in 
contrast to the paleocerebellum, which is of principal importance for the trunk. 
Ablation of the neocerebellar structure, 'especially when the dentate nucleus is 
involved, causes errors in force and rate of movements, also errors in range and 
direction of movements. Hypotonia is an enduring symptom in man after cere- 
bellar destruction. 

Of great importance in man is the compensation made by the cerebral cortex 
for cerebellar destruction. Surgeons do not hesitate to remove portions of the 
lobes in an approach to deeper structures, and the general rule applies that, unless 
a lesion of the cerebellum is progressive, the patient overcomes the symptoms of 
cerebellar deprivation. Bailey has shown an ontogenetic relation between the 
frontal lobe and the contralateral cerebellar lobe. 

Vol. VI. 1245 



26 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

Innumerable efforts have been made to summarize the function of the neo- 
cerebellum in a single word. The nearest approach to success in that effort is 
the word synergy; the term for symptoms of deprivation is asynergy. This word 
means " without working together " and applies to muscular function. 

It will be recalled that the principle of reciprocal innervation is ascribed 
mainly to the spinal cord, that is to say, patterns in the spinal cord cause the 
antagonists of any group of muscles to relax when the muscles in question con- 
tract. That the cerebellum also functions in this way is evident from the dis- 
turbance of reciprocal innervation which appears, when a progressive lesion of the 
cerrebellum occurs, for example, in the disease known as olivo-ponto-cerebellar 
atrophy or in a hereditary cerebellar ataxia. However, once any disease of the 
cerebellum becomes stationary, the spinal mechanisms are almost self-sufficient 
in managing reciprocal innervation. 

Mesencephalon 
(Midbrain) 

The mesencephalon is a small portion of the brain stem only three-quarters 
of an inch in length between the pons below and the hypothalamus above. It 
contains structures of vital importance to the " power plant " of the individual 
inasmuch as destruction of the periaqueductal gray matter removes all tendency 
to spontaneous movement from the individual (cats and chimpanzee experiments, 
Bailey and Davis^), and the centers for waking and sleep are partly located there. 
Anatomically it includes the cerebral peduncles, the entrance of the superior 
cerebellar peduncles into the brain stem, the corpora quadrigemina, the red nuclei, 
the substantia nigra and the third and fourth cranial nerve nuclei. It is the center 
of the mesencephalic outflow of the cranial autonomic system. On the median 
sagittal section of the brain the mesencephalon may be visualized as that portion 
between two lines of section, the upper of which passes from the anterior margin 
of the superior colliculi to the posterior border of the mammillary bodies, the 
lower of which passes from the inferior border of the quadrigeminal plate to the 
anterior border of the pons. The upper of these sections, when made in an experi- 
mental animal, produces decerebrate rigidity. Such an animal is commonly known 
as a midbrain animal. 

Contrary to age-old teaching, the synaptic center for pupillary light reflex 
does not pass through the superior corpora quadrigemina but through a small 
area just anterior (ventral) to them (Fulton^). The center for pupillary con- 
striction is the Edinger-Westphal midline nucleus of the third nerve. 

The majority of the righting reflexes are integrated in the midbrain. While 
the neck righting reflexes are integrated in the medulla and the optical in the cor- 

VoL. VI. 124s 



MESENCEPHALON 



27 



tex, the labyrinthine righting reflexes, body righting reflexes acting upon the head 
and body righting reflexes acting upon the body are integrated in the mesen- 
cephalon. 

There has been a great divergence of opinion concerning the function of the 




Fig. 12. Author's drawing from myelin sheath section, magnified. The section is slightly 
parasagittal through the brain stem. CC, corpus callosum; Fo, fornix; Ce, cerebellum; QP 
and QA, posterior and anterior corpora quadrigemina ; NH, habenular nucleus; Th, thalamus; 
NR, nucleus ruber ; SP, superior cerebellar peduncle ; Ma, mammillary body ; Ca, anterior com- 
missure; CTF, central tegmental fasciculus; ML, median lemniscus; Py, pyramidal tract; SPP, 
SSP, stratum profundum and superficialis of the pons respectively ; OCh optic chiasm ; 10, in- 
ferior olive. 

red nucleus in the mesencephalic righting reflexes (Fig. 12). The discussion has 
centered around the question whether it was the red nucleus itself, or neighboring 
structures, through which the reflexes acted. Magnus, the great master in this 
field, who received his inspiration from Sherrington, has produced a remarkable 
monograph entitled Korperstellung dealing with the subject. Rademaker^ wrote 
a good sized monograph called, " Die Bedeutung der roten Kerne und des iibrigen 
Mittelhirns fur Muskeltonus, Korperstellung and Labyrinthreflexe " in which the 
general region of the red nucleus was credited with much of this function. 

It seems that most of the difficulty in interpretation of physiology of the red 
Vol. VI. 1245 



28 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

nucleus stems from anatomical difficulties. It has been known for years that the 
inferior large-celled portion of the red nucleus gives rise to the rubrospinal tract, 
which crosses in Forel's decussation and descends into the spinal cord. This 
tract, however, is a delicate bundle, which has always seemed incapable of being 
the source of the large rubrospinal tract or of accounting for rubral influence on 
the anterior horn cells. 

On the other hand, the much larger central tegmental fasciculus, which suppos- 
edly has had its origin from the thalamus, has been shown by Spatz^" to arise from 
the parvicellular portion of the red nucleus at the supero-mesial angle. It makes 
its way as a large compact bundle, establishing relays with the tegmental reticular 
formation in the pons and medulla. It sends fibers to the inferior olive and con- 
tinues into the spinal cord in direct communication with the large ground bundle 
system. This rubro-spinal mechanism by its anatomical connections is peculiarly 
fitted to serve automatic extrapyramidal mechanisms. 

The large group of pigmented cells known as the substantia nigra is located 
ventral to the red nucleus and extends as a sheet in the cerebral peduncles. Its 
connections are with the corpus striatum and with areas 4 and 6 of the cerebral 
cortex. It is concerned with muscular tone, but its exact physiological role is 
not determined. It is the principal seat of inflammation in lethargic encephalitis. 

In the periaqueductal gray matter, in the superior portion of the mesen- 
cephalon and extending into the h3^pothalamus, is a center concerned with sleep. 
It may be looked upon as a structure which, when active, maintains attention and 
focuses consciousness, and which, when inactive, permits sleep. Its functional as- 
sociation with the diencephalon is so intimate that a sharp distinction is impossible. 
Its further discussion is reserved for a consideration of the hypothalamus. 

Vegetative Nervous System 

The vegetative nervous system is contained partly within the central nervous 
system, where it is represented in the cortex, thalamus, hypothalamus, mesen- 
cephalon, medulla and spinal cord, partly in a paravertebral chain of ganglia with 
subsequent ramification in a series of plexuses in or about the viscera and finally, 
in fibers distributed with the peripheral nerves. It is thus as extensive in its dis- 
tribution as are the brain and spinal cord with all their peripheral nerves. Fulton'* 
defines the system, although he calls it the autonomic nervous system, as " that 
part of the nervous system innervating smooth muscle, cardiac muscle and the 
glands." In general the vegetative nervous system serves the function of main- 
taining homeostasis (Cannon.) 

The peripheral distribution of the fibers may be described as consisting of two 
parts harmoniously antagonistic (to use an accurate, although apparently para- 

VoL. VI. 1245 



. KrPOTH»L AMWS 



NERVE 




Fig. 13. Scheme of the vegetative nervous system. (Modified from Greving, Handbuch 
der Neurologic, Bumke-Foerster, Springer, Berlin, 1936.) 
Vol. VI. 1245 



30 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

doxical, term), the cranio-sacral (greater vagal or parasympathetic) and the 
thoraco-lumbar (or sympathetic) outflow (Fig. 13). The antagonism may be 
illustrated by the action of the former in constricting the pupil, slowing the heart 
and increasing bowel activity and the action of the latter in dilating the pupil, 
increasing the rate of the heart and reducing peristalsis. Yet the actions of the 
two are coordinated beautifully to the ultimate benefit of the entire organism, 
any undue imbalance actually generating the clinical picture of illness. The 
entire subject of psychosomatic medicine rests on improperly controlled balance 
in some division of this system. 

Both divisions of the vegetative nervous system are characteristized by origin 
within the central nervous system and occurrence of one synapse along every 
path; thus one speaks of preganglionic and postganglionic fibers in every instance. 
In the parasympathetic system the preganglionic fibers are relatively long and 
have their synapses close to, or actually within, the organ supplied. They do not 
intimately reach the skin or body wall. Their action is discrete; they exert their 
force on certain organs (pupil, salivary glands, islands of Langerhans, external 
genitalia, bladder and rectum) and do not act en masse. In the sympathetic sys- 
tem the synaptic junctions, as a rule, lie in ganglia of the prevertebral chain or in 
ganglia of prevertebral plexuses, such as the coeliac and mesenteric plexuses. 
Each preganglionic fiber contacts a large number of postganglionic fibers, per- 
haps 20 or more, in contrast to those of the other system, in which they contact 
very few. The sympathetic acts en masse, thus putting a large part of the body 
into instant readiness in an emergency. 

Speaking in general, one may say that the parasympathetic system " presides " 
during peace, i.e. over anabolism, and hence is predominant during sleep. The 
pupils then are relatively smaller, blood pressure is lower, heart rate slower, blood 
sugar lower, perspiration greater. Emissions then occur, and excretions are 
prepared. The sympathetic system predominates during waking hours and hence 
during catabolism. The body is keyed up for its contest with the outside world, 
for fight or flight. 

The action of this portion of the system may be mimicked by injection of 
adrenalin; the pupils dilate, tachycardia appears, blood pressure is elevated, blood 
sugar rises, gastric secretion is suppressed, excretion of feces is suppressed also 
unless the whole organism is paralyzed with fear, and all reproductive functions 
are abolished. 

The sympathetic division differs anatomically from the parasympathetic in 
having white rami communicantes. through which the efferent motor fibers leave 
to enter the sympathetic chain of ganglia. Through gray rami other fibers re- 
enter the nerve to be distributed with it. 

Vol. VI. 1245 



VEGETATIVE NERVOUS SYSTEM 31 

Communicantes Vegetative Nervous System within the Spinal Cord 

The cells of origin of the vegetative nervous system within the spinal cord are 
found in the lateral cornua of the gray matter. The preganglionic fibers for the 
thoraco-lumbar outflow (sympathetic) emerge from the first dorsal to the second 
lumbar segments inclusive. They run in the anterior (motor) root until a point 



POSTERrOR ROOT 



-SPINAL GANGLION 




SYMPATHETIC NERVE 

POST. SYM GANGLION - 

GANGLION OF SYM VERTEBRAL 
CHAIN 



SPLANCHNIC NERVE 1 . 
TO KIDNEYS . 



-SPINAL NERVE POST 



SPINAL NERVE ANT 



•V^__TO VASOMOTORS 
""^^.TG SWEATGLANDS 
V TO PILO ERECTORS 



RNOOAL RAMUS 



TO LIVER ^ 

TO eOWEL - _^ 




-TO PREVERTEBRAL GANGLIA 



SEMILUNAR GANGLION 

Fig. 14. Scheme of the course of fibers in rami communicantes. (Modified from Graving, 
Handbuch der Neurologie, Bumke-Foerster, Springer, Berlin, 1935.) 

is reached in the peripheral nerve beyond the gray ramus, then flow out in the 
white rami communicantes to a synapse at the same level, or higher or lower 
levels before a synapse is reached. After a synapse the liber reenters the nerve 
from the sympathetic chain through the gray ramus to be distributed with it. 
In the cervical region there are no sympathetic emergent fibers; those for the 
head emerge through the upper dorsal segments and ascend in the cervical sympa- 
thetic trunk. There are usually three cervical ganglia, and fibers continue upward 
from the superior cervical ganglion to be distributed through the (sympathetic) 
carotid nerves. The dilator fibers for the pupil, for instance, arise in the hypo- 
thalamus, pass downward through the entire brain stem and cervical cord to the 
Vol. VI. 1245 



32 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

first and second dorsal segments, then ascend through the sympathetic trunk to 
the superior cervical gangHon where the first synapse occurs (Figs. 14 and 15). 
The fibers then ascend through the internal carotid nerves to where they can join 
the superior division of the trigeminal nerve to the orbit. 




DILATATION 
OF PUPILS 



VASO- 
COMSTRlCTlON 



Fig. 15. Course of preganglionic fibers as determined by the nicotine method. 
(From Greving, Handbuch der Neurologie, Bumke-Foerster, Springer, Berlin, 1935.) 

The fibers for the sacral outflow arise from the lateral horns as do the sym- 
pathetic fibers and make their exit from the second to the fifth (sometimes only 
from the third and fourth) sacral segments. They depart from the corresponding 
nerves and go in separate nerve bundles, called the nervi erigentes, and form their 
first synapses within ganglia of the pelvic plexuses or within the walls of the rectum 
or bladder. 



Vol. VI. 124s 



DIENCEPHALON 33 

Vegetative Nervous System within the Medulla Oblongata 

Vegetative centers within the medulla oblongata consist of the superior and 
inferior salivary nuclei and the dorsal vagus nuclei. Through the vagus nerve 
fibers reach the heart, bronchial tree and the gastrointestinal tract as far as the 
transverse colon. Irritable carotid sinus is a syndrome sometimes resulting in 
epileptiform seizures. Section of the ninth nerve at the medulla recently has re- 
lieved that condition. 

DiENCEPHALON 

(Hypothalamus: Thalamus: Subthalamus) 

The importance of the diencephalon. and especially of the hypothalamus, in 
the life of the individual is just coming to be fulh' recognized. While without any 
cerebral cortex an individual (anencephalic monster) may exist, breathe, cry, eat 
and sleep, without a hypothalamus he will die unless kept alive by artificial means. 
In the hypothalamus are integrated the highly organized visceral and somatic 
reaction patterns, which are essential to life itself. 

Here it should be clarified that a decorticate animal (one deprived of its 
neocortex) as a result of the operation, inevitably will lose more than the cortex, 
for the simple reason that the thalami, except for the most mesial portions, will 
degenerate. A decorticate animal, therefore, like an anencephalic monster, is 
deprived of much of its diencephalon. The portion of the diencephalon remaining 
is essentially the hypothalamus and subthalamus. 

Hypothalamus 

Without any cerebral cortex an individual still show's emotions of a sort; the 
sham rage of the decorticate animal or of the animal, whose hypothalami are be- 
ing stimulated by electrodes, is classic. Without hypothalamus there is no emo- 
tion. One might state the matter differently and say that the hypothalamic 
patterns are the neuronal structures essential to emotion. And inasmuch as all 
behavior is emotionally motivated, it follows that the hypothalamus with the 
periaqueductal gray matter is the " power house " of the body; it is the source 
of all dynamics. Corroboration has come recently from the field of electroen- 
cephalography, as Obrador" and Kennard^'- independently have shown that, 
when the h\-pothalamus is destroyed, all electrical activity of the cortex ceases. 

Masserman^^ has produced only sham rage by stimulation of the hypothal- 
amus with fixed electrodes. After the sham rage, it was found, conditioned re- 
flexes, which had been established before the stimulation, were not lost. This is 
evidence that the feeling tone was not aroused, and on that basis Masserman 

Vol. VI. 1245 



34 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

concludes that sham rage is not true emotion. Since only sham rage is elicited 
by hypothalamic stimulation and not the appropriate feeling tone, Masserman 
concludes that the hypothalamus is not the seat of the emotions. 

There are several important objections to such conclusions. In the first place 
only a small portion of the hypothalamus was thus stimulated and that portion 
was not the same as that stimulated by Foerster; traction on the hypothalamic 
floor did result in arousing of feeling tone. In the second place, it evidently makes 
quite a difference whether the impulses are started from an electrode or by simple 
traction or by rubbing. It is to be recalled that sponging of the anterior floor of 
the third ventricle caused sexual pleasure in one of Foerster's patients, while in 
another compression of the posterior part by a tumor caused emotional depression. 
But in that location rubbing or traction did not give the symptom; only com- 
pression did so. Further, feeling tone is not the only element of emotion; all the 
appropriate vegetative reactions help to make up the whole pattern, and the 
presence of the intact cortex greatly elaborates it. 

As is usual, when emotions of investigators are aroused in scientific discussions 
about interpretation of observations; the difficulty lies in the lack of exact defi- 
nitions. What is emotion? Masserman regards emotion as feeling tone. He 
considers sham rage devoid of emotion, because the feeling tone either ceases 
immediately, when the stimulus producing the sham rage is removed, or because 
there is no feeling tone at all. His principle seems to be that feeling tone cannot 
cease suddenly. Yet it is common experience that certain types of persons fly 
into a rage and become calm instantly upon removal of the stimulus which causes 
the emotion. It is also common experience to see persons of another type who 
cannot become calm for days. The duration of the feeling tone should, therefore, 
not be a criterion to determine whether or not emotion is present. Emotion is far 
more than feeling tone ; it embodies consciousness of it in most instances and also 
memory of it, plus all of the visceral and somatic manifestations of it. 

What seems to the writer crucial evidence that the engrams of emotion are 
located basically in the diencephalon consists of two facts: (i) the human infant 
shows emotion at birth, yet there is no myelination of any of the association fiber 
systems of the brain; (2) the normal infant at birth does not have electroen- 
cephalographic waves except " irregular show waves with a frequency of one half 
to two per second " (Berger, Davis and others, see Gibbs and Gibbs^^). 

Dissociation of the vegetative reaction from feeling tone is well known clini- 
cally. In a case of parkinsonism with pseudobulbar palsy observed by the writer 
the patient showed marked involuntary crying. When asked whether he had the 
appropriate tone the patient replied, " Goodness no! When I get to crying I look 
in the mirror and laugh at myself crying ". Patients with pseudobulbar palsy 
also may start laughing and be unable to cease, even though they are embarrassed 
Vol. VI. 1245 



DIENCEPHALON 35 

by the display. The ability, therefore, of an experimenter to produce one com- 
ponent of emotion without the other does not prove that the engrams of emotion 
are not located in the area stimulated. 

Further evidence in the same direction is available in normal persons daily. 
Many men are perfectly capable of strong sex desire and even gratification as a 
purely mechanical act without any material component of feeling tone. Instances 
are numerous of men, after paying a prostitute for sexual satisfaction for a long 
period of time, finally " falling in love " with the woman, i.e. developing a feeling 
tone, which then completes the emotion. All of the well-known " love-making '' 
of the stage and screen depends on the ability of the player to go through the 
act without having the feeling tone. 

Much evidence has appeared to show that the hypothalamus is also the seat 
of the patterns constituting personality. Human infants show personality at 
birth, yet the brain is not myelinated above the diencephalon in any association 
areas. Litter puppies and kittens at birth show personality differences, and inas- 
much as the cerebral cortex is a blank state with association tracts unmyelinated 
and with no records of any experience at the time of birth, the engrams of per- 
sonality must reside below the cortex. Hypothalamic lesions of lethargic en- 
cephalitis notoriously cause changes of personality. Neoplasms affecting the 
walls of the third ventricle almost regularly cause personality changes. Psychia- 
trists find that the constitutional psychopathic personality is almost entirely 
refractory to alteration because personality depends on congenital reaction pat- 
terns, not on cortical patterns, which are the result of training and subject to in- 
tellectual control (see The Hypothalamus, Assoc. Research Nerv. and Ment. Dis., 
1939, especially the paper by Alpers^^). 

The hypothalamus with the anterior part of the mesencephalon is the center 
of consciousness; when the hypothalamus is out of function, the individual is in 
coma regardless of intactness of the entire cortex. In the metaphor used above, 
in which the hypothalamus was called the power house of the body, the simile is 
apt that, when the power is off, the factory cannot function, even though the entire 
office staff is present. If an intermediate connection is broken, as when the 
thalamus is out of function bilaterally, the result is almost the same so far as 
capacity for function is concerned. Stern^- has reported a case with bilateral de- 
generation of the thalamus as the only lesion. The patient first showed hyper- 
somnia, then progressive dementia and finally coma. Many clinical cases have 
now made clear that lesions in the thalamus cause a profound disturbance of 
attention, and attention is the focus of consciousness. 

As the diencephalon is the seat of the emotions, it follows that, as stated, it is 
the seat of motivation. It is, therefore, the seat of purpose in life; it is the basis 
of all instinctive drive^ all behavior. 

Vol. VI. 1245 



36 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

Coming down to the physiological functions, which underlie behavior, we find 
the hypothalamus to be the fundamental regulator of visceral and somatic physio- 
logical correlation. Its presence is essential to the maintenance of blood pressure, 
pulse rate, respiration rate, body temperature. It regulates blood sugar, fat and 
carbohydrate metabolism in general and some constituents of the blood chemis- 
try. As it largely governs the pituitary gland, it largely controls the entire en- 
docrine system; it regulates sex function and libido, growth, the metabolic rate, 
hunger and thirst, water metabolism, in a measure the blood cell level and the 
orderly function of the gastrointestinal tract. One might generalize and say that 
it governs, by virtue of its being the seat of the primary neurons of it, the entire 
sympathetic nervous system. 

While the sympathetic neuronal patterns are, in general, more scattered than 
the parasympathetic ones, the posterior nuclei are more concerned with the former, 
and the middle and anterior more with the latter. 

It is true that there are cortical areas, which by stimulation have been shown 
to exert influence on vegetative functions, but this influence is of minor im- 
portance; the hypothalamus is the center of the system, and while the cortical 
level is in a sense " above " it, it is of only secondary value to the body in the 
function of visceral regulation. 

Foerster^*' and later others have shown that irritation of the anterior portion 
of the floor of the third ventricle causes hypomanic activity with disturbance of 
judgment, ribald laughter, etc., all of which ceases when the irritation is removed 
(see paper by Alpers^'^'). Pressure of tumors on the posterior portion produces 
moroseness and dullness. In the posterior portion adjacent to the mesencephalon 
lesions produce sleep and stupor going on to coma. Here we may correlate the 
fact that the anterior patterns are more concerned with parasympathetic function, 
left intact in such lesions, and predominate during sleep, while the sympathetic 
functions, destroyed by such lesions, are largely submerged during sleep. 

From anterior and midline nuclei in the region of the tuber cinereum there 
are evoked bladder contractions, cardiac inhibition, increased peristalsis of the 
stomach and bowel and sweating to control body temperature. Blood sugar also 
is regulated here, and destruction of the supraoptic nuclei causes diabetes in- 
sipidus. Occasionally lesions in this area upset body chemistry to cause diabetes 
mellitus without ketosis and may give the symptoms of urinary retention, thus 
simulating uremia. Even fat metabolism may be disturbed by lesions of the 
hypothalamus leading to obesity or cachexia. 

Cooling of the hypothalamus causes pilo-erection and shivering, while heating 
may result in sweating or hyperthermia. Traumatic lesions may cause the latter 
also. 

The clinical syndromes which may be evoked from the hypothalamus either 
Vol. VI. 1245 



DIENCEPHALON 37 

by irritation or destruction have been listed by Riddoch as follows: (i) diabetes 
insipidus, (2) bulimia, (3) glycosuria with or without hyperglycemia, (4) obesity 
and cachexia, (5) sexual disorders, amenorrhea, impotence, loss of, or increase of, 
libido, adiposogenital syndrome, (6) sleep disorders including narcolepsy, (7) 
thermal dysregulation, (8) polycythemia or leukocytosis, (9) ulceration of the 
upper alimentary tract, (10) autonomic diencephalic epilepsy and (11) emotional 
disorders. 

With the development of the cerebral cortex fiber connections have been 
established with the diencephalic centers. The cortical centers for autonomic 
regulation are located close to the somatic centers for the same functions. Thus, 
cardiovascular reactions have been obtained from Brodmann areas 4 and 6, 
obviously to stimulate vegetative responses to motor activity. In such situations 
both sympathetic and parasympathetic centers are located together, as both vaso- 
constriction and vasodilation can be obtained by electrical stimulation of areas 
4 and 6. The frontal region also is capable of influence on peristaltic function, a 
necessary relaxation for volitional influence on eliminative function. 

Thalamus 

Within the last decade the thalamus has been studied repeatedly and inten- 
sively by a number of men including Clark^^, Papez-'- and Walker-\ and a consider- 
able reorientation has resulted. A combined anatomophysiological summary may 
be given as follows: The anteroventral nucleus (Walker's terminology) receives 
fibers from the mammillo-thalamic tract and projects to the cingulate gyrus and to 
the paracentral lobule. From the cingulate gyrus fibers go to the orbital cortex. 

The dorso-median nucleus is a relatively large mass bluntly pointed anteriorly, 
swelling to a considerable width in the central portion and bifurcated posteriorly, 
where it appears on both sides lateral to the habenular nuclei. The mesial por- 
tion is magnocellular; the dorsolateral is parvocellular. The large-celled portion 
seems to be the connecting link between the periventricular gray matter of the 
hypothalamus and the orbital portion of the frontal lobes. Here, then, is the 
thalamic portion of the engram system of personality. The small-celled part 
projects to areas 9, 10 and 12 of Brodmann. The lateral posterior nucleus is 
linked similarly, but the parietal cortex is the portion with which connections are 
made. The centromedian nucleus is connected closely with these nuclei in the 
thalamus, but it does not project to the cortex. 

The large, anteriorly placed, ventrolateral nucelus receives the fibers of the 
brachium conjunctivum (superior cerebellar peduncle) direct from the dentate 
nucleus and projects to areas 4 and 6 of Brodmann. It is through this connec- 
tion that the cerebellum regulates motor cortical functions. 

Vol. VI. 1245 



38 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

The large posteroventral nucleus and the arcuate nucleus are organized alike. 
The latter serves for the facial and laryngeal areas including the organs of taste 
and the trigeminal area. The former serves for the body below the face; the 
spinothalamic tract terminates behind the site for the median lemniscus. This 
nucleus projects to the postcentral convolution ; lesions between it and the cortex 
cause only hypesthesia; lesions within the thalamus may cause anesthesia and 
" central pain ". 

The posterior portion of the thalamus includes the pulvinar and the geniculate 
bodies. The lateral geniculate is a way station for vision; a lesion of it causes 
homonymous hemianopia. The median geniculate body serves similarly for hear- 
ing, but as fibers from both cochlear ganglia project equally to both median 
geniculates, a lesion of one does not cause deafness in either ear. 

Subthalamus 

The region known as the subthalamus is bounded superiorly by the thalamus, 
anteriorly by the hypothalamus with which it merges imperceptibly, inferiorly by 
the mesencephalon and laterally by the cerebral peduncle as it ascends to become 
the internal capsule. It contains the corpus subthalamicum of Luys, part of the 
substantia nigra, part of the zona incerta and many fiber tracts. The body of 
Luys is important because a lesion in it gives rise to hemiballismus of the opposite 
upper limb. The mesial portion of the subthalamus is somehow concerned with 
retention of basic consciousness because hemorrhage into it bilaterally or severe 
inflammatory reaction produces coma. 

Corpus Striatum 

The corpus striatum consists of the caudate nucleus and the lenticular nu- 
cleus. The latter consists of the putamen and the globus pallidus. The chief 
connections are with the thalamus, the body of Luys and the substantia nigra. 
The physiology is imperfectly known, yet it is clear from clinico-pathological and 
phylogenetic studies that the corpus striatum has an enormous influence on the 
physiology of the general motor mechanism. 

The cerebral cortex is a recent phylogenetic acquisition, yet lower vertebrate 
forms without any material quantity of cortex have adequate motor function for 
their purposes. Myelogenetic studies, classically those of Flechsig, show that in 
the new born infant the corpus striatum is fully myelinated, while the pyramidal 
tract is not developed to functional capacity. It is generally believed that the 
human intrauterine motor activity is mediated by the extrapyramidal system, and 
it seems evident from observation of the normal infant during the first few months 
Vol. VI. 1 245 



CORPUS STRIATUM 



39 




Par 



/j SUBCORTICAL t^ 
jr"; CENTERS ;fe 



PALLIDO - SUBTHALAMIC 



^Ito 

^V SPINAL 
"^^J CORD 



Fig. i6. Bucy's scheme to illustrate the cortical-basal ganglionic functional interrela- 
tionships. (Redrawn from Bucy, The Precentral Motor Cortex, Univ. Ills. Press, Urbana, 
I944-) 

of the life that the gradual withdrawal of extrapyramidal control in favor of pyram- 
idal occurs as the new system becomes myelinated. 

There is also an experimental approach to the problem. Dr. Kennard^- has 
decorticated monkeys, both old and young, and she has severed the pyramids at the 
medulla in both old and young. While the older animals have great difficulty in 
adjusting to such violent subtractions from their motor mechanisms, the young 
ones do surprisingly well. It is evident that extrapyramidal mechanisms are 
adequate to permit purposeful movements. 

Dr. Sarah Tower (Bucy^") has done similar and also additional independent 
Vol. VI. 1245 



40 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

work. Notably she has sectioned the pyramids without producing complete 
paralysis of voluntary movement. Her conclusions are that stereotyped move- 
ments generally are initiated by the extrapyramidal system. 

In harmony with these phylogenetic, ontogenetic and experimental studies are 
the findings on human material by such men as Jakob--, Wilson-", the Vogts, 
Bonhoeffer and others studying clinico-pathological cases. In the former group 
of studies the material consisted chiefly of cases of cortical absence or deficit ; in 
the latter group the opposite approach is taken by the study of destruction or 
deficit of the corpus striatum. The classical paralysis agitans throws a great deal 
of light on the subject. 

Patients with paralysis agitans suffer chiefly with degeneration of the projec- 
tion fiber system of the globus pallidus. Now, that system does not project 
directly to the spinal cord but instead to the thalamus and the corpus subthal- 
amicum of Luys, then back to the inhibitory areas of the motor cortex. Yet the 
effect of degeneration is manifest in the types of movements of which the patients 
are capable or incapable. The abnormalities may be studied in two groups of dis- 
turbances, tonic and phasic. 

Bucy^' has worked out a system which explains the tonic phase of disease of 
the corpus striatum (Fig. i6). He invokes the recently discovered suppressor 
strips of cerebral cortex, notably the ones known as 48 between areas 4 and 6 
and 88 anterior to area 6 of Brodmann. These areas have, by stimulation, a sup- 
pressor effect on areas 4 and 6, which in turn have connections with the anterior 
horn cells through undetermined subcortical centers. 

By an elaborate anatomical and physiological analysis of the known mecha- 
nisms Bucy explains choreoathetosis and tremor, the disturbances of the 
tonic phase of the ganglionic disease. In brief, he considers the abnormal move- 
ments to be the result of removal of inhibition of the frontal extrapyramidal 
cortical areas. 

For an explanation of the phasic disturbances of paralysis agitans and more 
or less similar diseases of the basal ganglia we are indebted to the studies of 
Jakob, Wilson and others and the corroborative experimental evidence of Ken- 
nard and Tower. 

To review the first, the clinical evidence of the phasic manifestations, from cases 
of marked paralysis agitans I wish to present the following: 

The patient loses his ability to perform habitual acts and to make habitual 
movements. Above all, he loses power to initiate acts and movements. There is 
difficulty in planning an act, because he has lost one of his mechanisms. He can- 
not start to walk, and when once started, he cannot walk normally; he shuffles 
his feet. If he wishes to turn over in bed, he cannot " figure out " how to do so. 
He cannot initiate the movements of feeding himself, of rising from his chair or 

Vol. VI. 1245 



CORPUS STRIATUM 41 

of taking a step. If once started walking, he cannot initiate a change; he cannot 
stop. Hence the propulsion and retropulsion. 

He has lost his automatic association movement patterns. He does not swing 
his arms in walking, does not put his feet close to the seat nor support his weight 
by placing his hands on the chair on rising, does not throw his head back to look 
directly up, etc. He has to give thought to all these movements and acts. 

His posture also is peculiar in that it is dependent on weakness of the anti- 
gravity muscles. There is characteristically a long sweeping kyphosis of the 
upper dorsal spine and a tendency to flexion of the knees and elbows. The mouth 
tends to drop open. The finger postures are not so clearly related to weakness 
of antigravity muscles; the phalangeal joints are extended, the metacarpo- 
phalangeal joints flexed, the thumb extended. It is tempting to assume that the 
extrapyramidal system innervates the red musculature, but as all systems use 
the final common motor pathway, such a selectivity is unlikely, although not im- 
possible. Certain anterior horn cells might send their axons to the red, while 
others send theirs to the white muscles. It is still true that the habitual contrac- 
tion of the antigravity muscles suffers in paralysis agitans. 

With all this obvious difficulty in the performance of habitual acts the patient 
with paralysis agitans can do the unusual. He can catch a ball about as well as 
he could before his illness appeared; he can run much better than he can walk; 
he can walk with an artificial gait such as a high steppage gait or with steps 
unusually long. Inasmuch as the cortical patterns are then used, he does not 
imitate his usual gait well; he caricatures. One of my patients, who played the 
piano daily but the violin only rarely, was afflicted with paralysis agitans. I had 
her try the violin, when she could no longer play the piano. To her surprise she 
could finger the strings very well. 

In all of this exposition one sees clearly that habitual movements and acts are 
not performed well in cases of disease of the basal ganglia, but rare movements, 
for which the cortex and the element of attention are used, are well performed. 
It was this generalization which led Jakob to believe that as acts became habitual 
they are relegated to the patterns in the basal ganglia. The situation seems to 
be the following: In earliest infancy the individual performs his acts crudely and 
only with the extrapyramidal system. As the pyramidal system becomes func- 
tionally active, it is used, not to initiate the movement (initiation remains with 
the extrapyramidal system), but to control it in the interests of doing new things 
requiring dexterity and accuracy. As soon as dexterity and accuracy have been 
attained, the attention no longer is necessary, and when that point is reached, the 
pyramidal tract is no longer necessary for that act. However, if the act is to be 
modified or improved, the pyramidal tract is again called into use by means of 
the attention. When any movement or act becomes habitual, the attention is no 
Vol. VI. 1245 



42 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

longer required; the pyramidal tract is little used, if at all; the act fatigues one 
very little, and it appears to be relegated to the extrapyramidal system. How- 
ever, it is not really relegated, it is merely left to itself without supervision of the 
pyramidal system. 

The extrapyramidal (striatal system) has one other function, which should 
be stated, namely inhibition of tone of skeletal muscles. In cases of section of 
the extrapyramidal tract, the deep reflexes are increased. This is in contrast to 
the effect on the deep reflexes of section of the pyramidal tract, which operation 
diminishes the tone. These facts have come to light through the work of Sarah 
Tower. » 

Pallium 

The pallium is defined as the cerebral cortex with its subjacent white matter. 
The cortex itself, only a few millimeters thick, is not entirely uniform even on 
gross inspection. The extent of the primary visual cortex can be discerned with 
the naked eye because of the stripe of Gennari, which is essentially a union of 
two bands of Baillarger. These white bands are simply zones in which association 
axons are located in layers. If the cortex is stained for cell bodies and examined 
under moderate magnification, it is seen that layers of cells are discernible, al- 
though the demarcation is not sharp in all instances. The importance of these 
facts lies in their physiological implications; the cortex is an organized layer of 
neurons with innumerable interlacing patterns and complexity of neuronal con- 
nections baffling imagination. Adjacent gyri are associated by means of short 
fiber systems, the U fibers, and more distant ones by means of fibers of appro- 
priate length. The entire white matter consists of fibers which take their origin 
in the cortex except relatively few projection fibers arising from nuclear masses 
below. 

On the basis of cellular arrangement of the neurons in the cortex, cytoarchi- 
tectonic studies, and without any reference to physiology the entire cortex has 
been mapped out into areas (Fig. 17). This was done first by Brodmann, later 
much more in detail by Economo and Koskinas-^, also by the Vogts and by Camp- 
bell. Bailey and von Bonin'-'^ and others recently have made new contributions. 
These cytoarchitectonic areas are not sharply delimited in every instance ; several 
observers working simultaneously do not agree upon the exact line of transition 
from one to the next. On reflection one would e.xpect such gradation, because 
each must be able to associate with its neighbor and, therefore, must merge. 

Sulci and gyri do not by any means always constitute the borders of cyto- 
architectonic areas, for which reason one cannot simply place numbers on the 
gyri. A separate map must of necessity be made, one in which the gyri are indi- 
cated merely for convenience of anatomical correlation. The central sulcus does 

Vol. VI. 1245 



PALLIUM 



43 





Fig. 17. Brodmann's cytoarchitectonic cortical areas. 



Vol. VI. 1245 



44 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

separate areas, but the calcarine fissure does not, although they are both primary 
fissures. 

The great master of neurology, Hughlings Jackson-'', postulated many im- 
portant neurological principles in the realm of physiology and also of clinical 
neurology, which have been verified since then. He understood thoroughly the 
principles of division of labor in the cortex particularly as related to motor func- 
tion. Dusser de Barenne, Bailey and many workers at the Yale University 
physiological laboratory' have established by the physiological method certain 
interrelations between cytoarchitectonic areas which have not been shown clearly 
anatomically. Thus, a certain area may " fire " another at some distance, while 
the charge does not function in the opposite direction. 

The Vogts, Dusser de Barenne, Tower" and others have shown in experimental 
animals that certain narrow strips of cerebral cortex respond to electrical stimu- 
lation only by inhibiting other areas. Carol and Bucy-^ recently have observed 
the same fact in the human subject. Whether or not these suppressor strips can 
be shown to have a distinctive cytoarchitectural appearance does not seem a matter 
of great importance ; identical arrangement of cell layers might easily permit dif- 
ferent neuronal connections in such a way as to produce inhibition instead of 
stimulation. Thus we are confronted with the necessity of admitting that ap- 
parent identity of cytoarchitectonic structure does not preclude difference in clini- 
cal physiological function. Certain areas certainly have functions not related 
to perception or to motor activity, inasmuch as much of the cortex is utilized for 
planning, thinking in general, for formation of ideas and for judgment. And 
much of our information still is fragmentary. For these reasons it is still impos- 
sible to list each cytoarchitectonic area with its corresponding physiology, deficit 
syndrome and effect of stimulation. The available knowledge is outlined below. 

Occipital Lobe 

All of the occipital lobe is devoted to vision, visual associations and visual 
memory. There are three distinct spheres of activity, area 17, area 18 and area 19 
of Brodmann. 

Area 17, area striata (borders of the calcarine fissure), serves for primary 
visual perception (Fig. 18). Irritation causes flashes of light to appear; destruc- 
tion, bilaterally, causes blindness. 

Area 18, area parastriata, serves for recognition of visual images. On the 
basis of clinical-pathological material it is believed that the superior portion is 
more concerned with animate, the inferior with inanimate objects. Irritation of 
area 18 by the electrical current produces an image of a light standing still in 
the opposite visual field. It also causes the eyes to deviate away from the side 

Vol. VI. 1245 



PALLIUM 



45 



euNcut 

/ ', MACULAR VISION 



Optic Radiations 

Corpus Callosum 

Optic Thalamus 
Corp. genie, ext. 




-7 ^PERIPHERAL VISION 

Visual Word Center 
-8 



Auditory Word Center 



Vocal Word Center 



'«UAU 



Fig. i8. — Diagram of Visual Paths (Modified from Vialet). 

Lesion at i produces Blindness of one eye. 

Bi-temporal hemianopia. 
Bi-nasal hemianopia. 

R. hemianopia with hemiopic pupil reaction. 
" normal pupil reaction. 



" 3 and 3 

*• 6 

" 7 
" 8 



Loss of visual orientation and localization in space. 
Word-blindness. 

{/Courtesy of Edward Arnold, Publisher) 



Fig. 18. Diagram of visual paths. (From Purves Stewart, Chapt. I, Vol. 
vi, Oxford Medicine, Oxford Univ. Press, New York, 1926.) 



Vol. VL 1245 



46 ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

stimulated. Destruction (bilaterally) renders the patient unable to recognize 
any object seen, causes visual agnosia for objects. 

Area 19, area peristriata, serves for revisuaUzation of images. As for area 18, 
in area 19 there seems to be a division of function, the superior portion serving 
especially for animate, the inferior especially for inanimate objects. Irritation 
causes visual hallucinations in the opposite half fields, destruction, loss of power 
of visual reminiscence in the visual sphere. The patient may have autotopagnosia, 
complete or partial, or may visualize animate objects including his own body, 
while failing to revisualize his home, streets and geography in general. 

Temporal Lobe 

The neopallial temporal cortex is devoted to hearing and to auditory asso- 
ciations in general. These include sounds in general, music and spoken language. 
The farther one withdraws downward and backward from Wernicke's area, the 
more interpretation is involved. 

Area 52 of Brodmann, the transverse temporal gyri, serves for auditory per- 
ception. Results of irritation are not directly known, because the area is inacces- 
sible to stimulation. Destruction causes total deafness. Unilateral destruction 
causes no appreciable loss of hearing, because both areas receive fibers from 
both ears. 

Areas 41 and 42 (functional distinction is not possible), area of Wernicke, 
serve for recognition of sounds except musical ones. Irritation (Foerster^*') 
causes hallucinations of hearing voices. Destruction causes total lack of recog- 
nition of sounds, auditory agnosia. Unilateral destruction causes auditory ag- 
nosia, word deafness, only, if the major side is destroyed. 

Area 38, anterior portion of the superior temporal convolution, serves for 
recognition of musical sounds. Irritation in some clinical cases has caused musi- 
cal hallucinations; results of electrical stimulation are not known. Bilateral de^ 
struction causes musical deafness. Unilateral destruction is soon recovered from. 

Areas 20, 21 and 22 serve for interpretation and recall of auditory impressions. 
Irritation causes auditory hallucinations; destruction causes incomprehension of 
spoken language. 

The uncinate gyrus and the temporal paleocortex in general are concerned with 
olfactory perception, recognition and recall; functional distinction between the 
various areas is not possible. Irritation causes olfactory hallucinations. It may 
be said that the uncinate gyrus is far more definitely concerned with smell than is 
the cingulate gyrus, pericallosal cortex. 

Area 37, posterior portion of the temporal cortex, is devoted to formulation 
of language (Nielsen-*) ; irritation has not produced recognizable symptoms, but 
Vol. VI. 1245 



PALLIUM 46(1) 

destruction of the major side or of both sides causes inability to marshal one's 
words to form sentences. One cannot recall names of objects. 

Parietal Lobe 

The parietal lobe, except the supramarginal and angular gyri, is concerned with 
general sensory perception, recognition and interpretation. It is divided into 
three portions, the postcentral gyrus and the superior and the inferior parietal 
lobules. The inferior lobule consists of the supramarginal (area 40) and angular 
(area 39) gyri, the latter of which has a highly specialized function entirely dif- 
ferent from that of the remainder of the parietal lobe (Nielsen-"). 

Areas i and 2 , postcentral gyrus, serve for primary perception of general sen- 
sation. Irritation causes contralateral paresthesias of numbness and tingling. De- 
struction causes hypesthesia and astereognosis. By virtue of its connections with 
the precentral gyrus irritation also causes Jacksonian seizures. 

Area 5 of Brodmann is not clearly understood. Its function seems related 
to the posture of the opposite lower limb inasmuch as stimulation causes flexion 
instead of extension of the contralateral lower limb. ' 

Area 7, superior parietal lobule, is concerned with elaboration of general sen- 
sory impressions, localization, recognition and interpretation. Irritation causes 
contralateral paresthesias of numbness and tingling. Destruction causes hyperes- 
thesia and astereognosis. The functional distinction between this area and the 
postcentral gyrus apparently is one of degree; lesions cause more disturbance in 
the postceritral gyrus than in the superior parietal lobule. 

Area 39, angular gyrus, is devoted to recognition and recall of visual images 
of letters, mathematical figures, musical notes, syllables and words. Results of 
irritation are unknown ; destruction of the major side or of both sides causes visual 
verbal and musical agnosia, alexia and, by virtue of loss of revisualization of the 
symbols, also agraphia. 

Area 40, supramarginal gyrus, is not entirely understood. Its cortex seems 
to form a special correlation center for planning of motor acts, upon the reception 
of the necessary sensory impressions. Results of irritation are not known, but 
acute destruction causes apraxia. When progression of the lesion ceases, the 
apraxia disappears. Even bilateral destruction does not cause lasting apraxia. 
This gyrus seems to form an important part of the " posterior association area " 
of Flechsig, 

Frontal Lobe 

The frontal lobes are among the last to have become even fairly well under- 
stood. The precentral gyrus and the speech area have been pretty well compre- 
VoL. VI. 1245 



46 (2) ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

hended for some time, but only within the last quinquennium have the " premotor " 
and " prefrontal " portions come within the bounds of comprehension. In gen- 
eral, the premotor portion of the frontal lobes is not concerned with formation of 
concepts; concepts are formed so completely in the posterior association area of 
Flechsig that both premotor areas may be ablated without loss of any memories. 
On the other hand, the anterior portion of the frontal lobes, through their intimate 
connections with the diencephalon, are of primary importance in wisdom. They 
utilize the concepts stored as engrams in the posterior portion of the brain, decide 
on the basis of past experience what is best for the future and thus modify, so far 
as modification is possible, the personality of the individual. 

Area 4, area gigantopyramidalis, constitutes a portion of the precentral gyrus. 
It is wide on the mesial surface and diminishes in width to almost zero near the 
sylvian fissure. This cortical area gives rise to a large part of the pyramidal tract, 
but the pyramids are not made up entirely of fibers from area 4. This tract is not 
the only source of corticospinal motor fibers, at any rate, because, after ablation 
of area 4, electrical stimulation of area 6 still provokes massive turning movements 
of the contralateral side of the body. The function of the fibers from area 4 is 
to perform accurate and fine (discrete), voluntary movements. Electrical stimu- 
lation provokes focal movements and, if electrodes of sufficiently small size are 
utilized, even the contractions of individual muscles, such as an interosseous of 
the hand, are obtained. One of Hughlings Jackson's greatest contributions to 
neurology was his analysis of the progression of movements down or up the body 
musculature upon irritation of the motor cortex. 

Tower^" recently has shown that the pyramidal tract has a tonic effect on 
the deep reflexes; its destruction diminishes them as already elucidated in an 
earlier portion of this chapter. 

Area 48 was not delineated by Brodmann but has been demonstrated physio- 
logically by Tower, b}^ Dusser de Barenne and McCulloch^** and others in animals 
and by Carol and Bucy-'' in man. It forms a narrow strip between areas 4 and 6. 
Electrical stimulation causes suppression of a voluntary movement already 
started. Destruction causes marked spasticity. 

Area 6 of Brodmann, prepyramidal motor cortex, causes upon electrical stimu- 
lation massive turning movements of the body toward the opposite side. The 
signs of its destruction in a normal person are not clear; in a patient with con- 
tralateral choreoathetosia its ablation tends to prevent the movements. 

Area 8 of Brodmann, located anterior to area 68, seems not to have a uniform 
physiology. Its lower end contains engrams for movements in writing and for 
turning of the head and eyes. The remainder is insufficiently understood, but 
Bucy has shown that it has a suppressor effect on voluntary movements. 

Area 43 of Brodmann, the pararolandic opercular area, certainly contains 

Vol. VI. 1245 



PALLIUM 



46(3) 



engrams for patterns of swallowing and chewing ; a unilateral lesion of the major 
side only causes dysphagia, an apraxia of swallowing. There is some evidence 
for the concept that the cortical sense of taste is located here, but I am skeptical, 
and Bailey '^ whose opinion based on cytoarchitectonic grounds is valuable, does 
not accept the idea. 

Area 44, Broca's convolution, is the seat of engrams of memory of how to move 
the vocal organs for purposes of speech. Stimulation causes repetitive speech 




tR POST ) 



ACS INF POST 



Fig. 19. Gross circulation of cerebrum and cerebellum, lateral view. 



without the will of the patient and destruction of the major side only, or of both 
sides, causes mutism until the other side is trained (Henschen^-, also Nielsen^^) . 

Area 45, pars triangularis of the third' frontal convolution, contains engrams 
of the patterns of motor musical function, both vocal and instrumental. Musical 
production by electrical stimulation has not been evoked, but ablation causes 
avocalia. 

The portion of the frontal lobe anterior to area 8 superiorly and to area 45 
inferiorly comprises areas 9, 10, 11, 12, 32, 46 and 47 and especially the " orbital 
cortex " and is concerned in a large measure with consciousness of self and with 

Vol. VI. 1245 



46 (4) ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

judgment. This analysis was stressed b}^ Kleist' ' in his study of war injuries of 
World War I, and the same theme is discernible in Brickner's''' analysis of his case 
of bilateral " prefrontal " lobectomy. It comes to the fore in striking degree in 
Freeman and Watts'^** analysis of their more than 200 cases of prefrontal lobotomy. 



A.CeR ANT 



V MAGNA GALtN K 




ACER A N T - 

CAR INT 

A COM POST 
A*CEP POST_ 
A CB SUP 



Fig. 20. Gross circulation of cerebrum and cerebellum, nesial view. 



Circulation of the Brain 

The cerebrum is supplied by blood almost entirely through the internal carotid 
and the posterior cerebral arteries. The internal carotid arteries give off the 
anterior cerebrals and continue as the middle cerebral arteries running up into the 
sylvian fissure. The two vertebral arteries unite to form the basilar artery, which 
lies along the anterior surface of the pons. The basilar divides into two to form 

Vol. VI. 1245 



CIRCULATION OF THE BRAIN 



46(5) 



- - A. COM ANT 



A CAR INT 
-A COM POST 




A CB MEDIA 
" CAUDITIVA) 

-A CB. INR ANT 

CA F05S. LAT bulb: 



Fig. 21. Gross circulation of cerebrum and cerebellum, basilar view. The tip of the 
right temporal lobe has been removed to display some of the deeper branches of the middle 
cerebral artery. 



the posterior cerebral arteries. These are shown in the illustrations (Figs. 19 
to 21). 

By means of the two posterior communicating arteries between the internal 
carotids and posterior cerebrals, and through the anterior communicating artery 
between the two anterior cerebrals the circle of Willis is formed. 

As shown in the illustrations (Figs. 19, 20 and 21 ) the middle cerebral arteries 
supply the entire lateral portion of the cortex as well as the corpus striatum except 
for a margin in the superior anterior one-half, which is supplied by the anterior 

Vol. VI. 1245 



46 (6) ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

cerebrals, and a similar margin in the posterior and inferior portions, which is 
supplied by the posterior cerebral arteries. The mesial surface of the hemispheres 
is supplied entirely by the anterior and posterior cerebral arteries. The inferior 
surface of the temporal lobes and nearly all of the occipital lobes receive their 
blood supply from the posterior cerebral arteries. The brain stem and cerebellum 
(surfaces and interior) receive their supply through branches of the basilar and 
posterior cerebral arteries. 

The anterior choroidal artery is a fairly large branch of the middle cerebral 
artery, which turns backward to supply much of the choroid plexus of the lateral 
ventricle. Its importance lies in the fact that it also supplies part of the thalamus 
and the posterior portion of the internal capsule. A lesion of it causes a focus of 
softening illustrated at 5 in Fig. 18. 

The general rule applies that the surface arteries, unless they are the seat of 
aneurysms, or unless they are traumatized, hardly ever rupture. On the other 
hand they are subject to thrombosis. The arteries, which receive part of their 
support from the brain substance, are the ones which commonly rupture. 

The surface venous drainage of the cerebrum takes place in two directions, 
upward to the superior sagittal sinus and downward to the lateral and sigmoid 
sinuses. The deep drainage from the ventricles is through the deep cerebral veins, 
vein of Galen and straight sinus to the torcular. The lateral ventricles are drained 
by means of the vena terminalis, which follows the curve of the caudate nucleus. 

The cerebrospinal fluid is secreted by the choroid plexus into the ventricles and 
is absorbed by the pacchionian granulations. It circulates slowly through the 
lateral ventricles and the foramina of Monro into the third ventricle. Thence it 
passes through the aqueduct of Sylvius to the fourth ventricle. Through the 
lateral foramina of Luschka and the median foramen of Magendie it enters the 
subarachnoid spaces of the brain and spinal cord. 

Anatomical Basis of Memory 

Memory is a function of all of the cerebral cortical neurons concerned with 
secondary and tertiary elaborations of sensory impressions and of all cortical 
areas concerned with association. The primary cortical areas of perception do 
not seem to possess the function of memory, because destruction of areas 1 7 and 
52 (vision and hearing respectively) leaves the affected person blind and deaf but 
with intact memory for all visual and auditory impressions. The prefrontal cortex 
may be destroyed without impairing memory; it appears to lack the function of 
memory but able to utilize memories for the benefit of the organism. 

Memory usually is considered a psychological function, but by a simple 
syllogism it can be made evident that pyschology is merely a branch of cerebral 

Vol. VI. 1245 



ANATOMICAL BASIS OF MEMORY 46(6-1) 

physiology. Thus, by definition all cerebral function is cerebral physiology. 
Psychology is a cerebral function; the brain is the organ of the mind as H. Charle- 
ton Bastian^* elaborated. Therefore, psychology is a branch of cerebral physi- 
ology. The only reason for any confusion has been that cerebral physiology has 
embraced all cerebral functions, which were understood, and the term psychology 
has been reserved for cerebral functions of so involved a character that man could 
not grasp them. Memory is now within the realm of physiology even in the classi- 
cal sense. 

Everyone will grant that, when one perceives an object, he " makes a mental 
note " of it. When he sees it, again he recognizes it. Further, when he performs 
an act or even a movement, he recalls later how he did it. That means that he 
has a memory of it. Physiologically speaking, when he sees an object, the im- 
pulses set up by the seeing travel over certain neuronal pathways, and when he sees 
the same object again and recognizes it, impulses travel over the same pathways. 
Those pathways are then called engrams, traveled neuronal pathways, and the 
engrams are the anatomical basis of memory of the seeing. Similarly, when he 
performs an act, he utilizes certain engrams, and those engrams are the anatomical 
basis of memory of the act. 

Now, any act is performed more easily the second time than the first and still 
more easily in subsequent attempts. A change must occur in the engram the first 
time it is used and also in subsequent functional activity. That change is the 
record of the performance and the anatomical basis of memory. It is probable 
that the changes are in the synapse to a greater degree than in the neuronal body 
or its projections, and the change is probably at first chemical, then physical and 
anatomical. 

If we apply this line of thought to Pavlov's^^ conditioned reflexes, we can see 
an anatomical basis for the psychological behavior of the subject of his experi- 
ments. Thus, the ringing of a certain bell or an identical bell comes to signify 
food. The dog will cock his head, turn his eyes and watch, then prepare to receive 
food, all in response to a sound, which he recognizes in his temporal lobe. The 
desire for food is a state of unsatisfaction in the diencephalon. When he feels 
that state, hunger, the sound is a signal that the hunger can be satisfied. If he 
has just eaten, he does not respond according to the same pattern. But, if he 
responds, the pathways can be traced as follows: Sound waves stimulate the 
tympanic membrane, impulses travel via the cochlear nerve and a neuronal chain 
to the median geniculate bodies, then to the gyri of the temporal lobes for percep- 
tion of the vibration rate. The adjacent cortical area, where memories of identi- 
cal sounds have been stored, recognizes the sound as identical with others which 
preceded satisfaction of hunger. Reflex impulses go over pathways to the quad- 
rigeminal plate, where appropriate movements of head and eyes take place. By 

Vol. VI. 1245 



46(6-2) ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

way of the tectospinal pathways impulses go to the spinal cord to give the dog 
his appropriate reflex support as he shifts the weight of his body and as he 
turns his head and prepares to walk toward or to the food. Simultaneously im- 
pulses go to the occipital lobe to awaken memory of the appearance of the food. 
All of the cortical areas stimulated send impulses to. and receive impulses from, 
the diencephalon. The hypothalamic centers for salivary and gastric secretion 
are stimulated, and impulses travel over the vegetative nervous system to the 
glands in question. Ordinarily this train of events is described as " sound of the 
bell starts glandular secretion ", and the phenomenon is called psychic con- 
ditioning. 

Neurological Basis of Psychiatry 

In harmony with the ancients in 1890 H. Charleton Bastian, the English neu- 
rologist, as mentioned, assembled enough material to conclude that " the brain is 
the organ of the mind ". With the advent of the sciences of vegetative neurology 
and of endocrinology a tendency to doubt Bastian 's thesis developed. It was 
clearly shown that pituitary and thyroid disturbances could easily upset the 
function of " the mind " to the extent of causing mental derangement. However, ■ 
with more extensive knowledge and more intensive study it has become increas- 
ingly evident that the brain actually is the organ of the mind. Pituitary dis- 
turbances, which cause mental derangement, can result also from hypothalamic 
neuronal disease affecting the pituitary gland, and thyroid disturbances, when 
they cause mental symptoms, act by causing a toxemia, which in turn affects 
the brain. 

As already indicated, disturbances of certain regions of the hypothalamus may 
cause stupor; of others, hypomanic excitement. Foerster has shown that mere 
gentle mechanical stimulation of the floor of the third ventricle may cause hypo- 
manic activity with disturbance of judgment lasting as long as the duration of 
the mechanical stimulation. 

It is well established experimentally as well as clinico-pathologically that cer- 
tain well-delineated areas of the cerebral cortex are concerned with perception, 
with recognition and with recall of visual, auditory and tactile impulses. The 
areas for taste and smell are not so definitely known. For the zones which are 
well known it is fully established that the areas for perception, if stimulated, will 
cause the patient to perceive the stimulus as specific for that modality of sensa- 
tion. The areas for recognition will, when stimulated, give rise to recognition of 
specific stimuli, and those for recall will arouse recall. Thus, if the visual area 
of recall is stimulated, the patient will see an object, which he has seen formerly, 
even though the stimulus is electrical. That is another way of saying that he will 
have a visual hallucination. Stimulation of any other area of the brain will not 

Vol. VI. 1245 



ELECTRICAL ACTIVITY OF CORTEX 46 (6-3) 

have a similar effect. In other words, visual hallucinations can result only from 
stimulation of the area for visual recall; auditory hallucinations can result only 
from stimulation of the area for auditory recall. From these facts as able a 
psychologist as McDougall and as able a neurologist as Henschen are agreed that 
all hallucinations result only from stimulation of the appropriate cortical area. 
The stimulus may result from a toxemia, a neoplasm, an abscess, a circulatory dis- 
turbance or from an electrical stimulation. It may be motivated from the 
hypothalamus and hence result from an emotional disturbance. 

This is not the place to elaborate on this subject in detail, but it is the firm 
conviction of the writer that eventually all psychiatric manifestations will be 
comprehensible on the basis of cerebral physiology. 

Spontaneous Electrical Activity of the Cortex 

Over a period of many years Hans Berger*'^', of Jena, studied by means of 
relatively crude apparatus certain electrical discharges from the cerebral cortex. 
The enormous technical difficulties in the work may be judged by the fact that 
up to about 1935 a full-time physicist specializing in electronics was required to 
maintain in good condition any such machine in daily active use. 

Berger discovered that a certain " basal condition " is essential to the record- 
ing of orderly waves whose interpretation is possible. That state is one of essen- 
tial mental rest with eyes closed but without sleep. Berger named the waves 
■alpha, beta, gamma and delta waves. At present the alpha rhythm still is called 
Berger rhythm, but the other terms have largely fallen into disuse, a terminology 
based on frequency and amplitude having replaced the literal designation. 

Alpha waves are predominantly occipital waves of about 10 per second rate 
and 10 to 75 millivolt amplitude. Beta waves are those about 25 per second 
frequency and 10 to 15 millivolt amplitude. Gamma waves are rapid and small 
waves, delta waves slow and large, as well as irregular. 

Berger himself showed that the electrical waves at birth were irregular and 
slow and that only with development did the adult pattern appear (at an age 
between 9 and 15 years) (Fig. 22). This harmonizes with the known facts of 
cerebral myelination. Gibbs and Gibbs have issued a valuable atlas of electro- 
encephalography to which the interested reader is referred for details. 

As stated previously, Abrador and Kennard independently have shown that 
all brain waves are extinguished upon complete destruction of the hypothalamus. 
The function of attention has an enormous influence on the waves; the mere 
opening of the eyes (visual attention) obliterates the occipital alpha rhythm. 
Demonstrators have shown upon themselves that enormous variability in waves, 
at the moment being recorded, can be produced by voluntary thinking of various 
Vol. VI. 1245 ^ 



46 (6-4) ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

situations. Gibbs and Gibbs" state (page 50) that: "The most extreme ab- 
normalities in the electroencephalogram may be unassociated with any clinical 
disorder, and on the other hand, a patient may have a clinical history of frequent 
seizures and yet show little in the way of interseizure disorder. He may even 

Fig. 22. Normal electroencephalogram above. Disturbances below after 
electroshock. Four simultaneous tracings were taken. 

have focal seizures involving one side of the face without loss of consciousness and 
show no change in the electroencephalogram ". Nevertheless, properly inter- 
preted, electroencephalograms are of great clinical value in neurology. 

The writer would like to comment on the expression '' unassociated with any 
clinical disorder ". Many conditions of the brain, obviously due to disease upon 
microscopic examination, can be present without clinical evidence of disease. 
Thus, the residuals of partial asphyxia at birth, tiny lesions due to rheumatic 
disease, those due to pertussis and other cellular abnormalities of vague etiology 

Vol. VI. 1245 



BIBLIOGRAPHY 46 (6-5) 

may easily be present without definable clinical manifestations. Thus, when one 
speaks of variability in " normal " electroencephalograms, one may be in con- 
siderable error in defining the normal. Electroencephalography still is too young 
a science to justify dogmatic statements concerning interpretations. 

BIBLIOGRAPHY 

1. RAMON Y CAJAL, S.: Histology, Wm. Wood and Co., Baltimore, 1933. 

2. ADRIAN, E, C: Conduction in peripheral nerves and in the central nervous sys- 

tem, Brain, 1918, XLI, 23. 

3. SHERRINGTON, C. S.: The Integrative Action of the Nervous System, C. Scrib- 

ner's Sons, New York, 1906. 

4. FULTON, J. F. : Physiology of the Nervous System, 2nd ed., Oxford Univ. Press, 

New York, 1943. 

5. TOWER, S. S.: Pyramidal and extrapyramidal mechanisms in the cortical control 

of movement. Meeting of Phila. Neurol. Soc, Oct. 23, 1942, Arch. Neurol, and 
Psychiat., 1943, XLIX, 782, also in BUCY, P. C: The Precentral Motor 
Cortex, Univ. 111. Press, Urbana, 1944. 

6. HINES, M.: in BUCY, P. C: The Precentral Motor Cortex, Univ. 111. Press, 

Urbana, 1944. 

7. LARSELL, 0.: The cerebellum: a review and interpretation. Arch. Neurol, and 

Psychiat., 1937, XXXVIII, 580. 

8. BAILEY, P. and DAVIS, E. W. : Effects of lesions of periaqueductal gray matter 

in cat, Proceed. Soc. Exper. Biol, and Med., 1942, LI, 51. 

9. RADEMAKER, G. G. J.: Die Bedeutung der roten Kerne und des iibrigen Mittel- 

hims fiJr Muskeltonus, Korperstellung und Labyrinthrehexe, Monographic aus 
dem Gesamtgebiete der Neurologic und Psychiatric, D. Foerster und K. 
Wilmanns, Heft 44, Berlin, 1926. 

10. SPATZ, H. : Handbuch der Neurologic, Bumke-Foerster, Springer, I, 474, Berlin, 

1935- 

11. OBRADOR, S.: Effect of hypothalamic lesions on electrical activity of cerebral 

cortex. Jour. Neurophysiol., 1943, VI, 81. 

12. KENNARD, M. A.: Effects on EEG of chronic lesions of basal gangha, thalamus 

and h>'pothaIamus of monkeys, Jour. Neurophysiol., 1941, VI, 405. 

13. MASSERMAN, J. H.: Behavior and Neurosis, Univ. of Chicago Press, Chicago, 

1943- 

14. GIBBS, F. A. and GIBBS, E. L. : Atlas of Electroencephalography, Published by 

the Authors, Cambridge, Mass., 1941. 

15. ALPERS, B. J.: Personality and emotional disorders associated with hypothalamic 

lesions, Assoc. Research Nerv. and Ment. Dis., Chap. XXVIII, p. 725, WiUiams 
and Wilkins Co., Baltimore, 1940. 

16. FOERSTER, O.: Handbuch der Neurologic, Bumke-Foerster, Vol. VL Springer, 

Berhn, 1936. 
Vol. VI. 1245 



46 (6-6) ANATOMY AND PHYSIOLOGY OF NERVOUS SYSTEM 

17. BUCY, P. C: The Pencentral Motor Cortex, Univ. 111. Press, Urbana, 1944. 

18. STERN, K.; Severe dementia associated with bilateral symmetrical degeneration 

of the thalamus. Brain. 1939, LXII, 157. 

19. CLARK, W. E. L., BEATTIE. J., RIDDOCH, G. and DOTT, N. M.: The Hypo- 

thalamus: Morphological, Functional, Chnical and Surgical Aspects, Oliver and 
Boyd, London, 1938. 

20. PAPEZ, J. W.: Summary of finer connections of basal ganglia with each other and 

with other portions of the brain, Assoc. Research Nerv. and Ment. Dis., 1942, 
XXI, 21. 

21. WALKER, A. E. : The Primate Thalamus. Chicago Univ. Press, Chicago, 1938. 

22. JACOB, A.: Die extrapyramidalen Erkrankungen, Springer, Berlin, 1923. 

23. WILSON, S. A. K.: An experimental research into the anatomy and physiology 

of the corpus striatum. Brain, 1913-1914, XXXVI, 427. 

24. VON ECONOMO, C. and KOSKINAS, G. N.: Die Cytoarkitektonik der Hirnrinde 

der erwachsenen Menschen, Springer, Berlin, 1925. 

25. BAILEY, P., VON BONIN. G. and ASSOCIATES: Functional organization of 

medial aspect of primate cortex. Jour. Neurophysiol., 1944, VII, 51. 

26. JACKSON, J. H.: Selected Writings of, ed. by J. Taylor, Hodder and Stoughton, 

London, 1931. 

27. GAROL, H. W. and BUCY, P. C. : Suppression of motor response in man, Arch. 

Neurol, and Psychiat., 1944, LI, 528. 

28. NIELSEN, J. M.: Aphasia, Chap. X, Vol. VI. Oxford Med., Oxford Univ. Press, 

New York, 1944. 

29. NIELSEN, J. M.: Agnosia, Apraxia, Aphasia, Los Angeles Neurological Society, 

Los Angeles, 1936; also in Textbook of Clinical Neurology, Hoeber, New 
York, 1 94 1. 

30. DUSSER DE BARENNE, J. G. and McCULLOCH, W. S.: Suppression of motor 

response upon stimulation of areas 4-s of the cerebral cortex. Proceed. Am. 
Physiol. Soc, Apr. 26-29, 1939, Am. Jour. Physiol., 1939, CXXVI, 482. 

31. BAILEY, P.; Unpublished work, personal communication. 

32. HENSCHEN, S. W.: Klinische und anatomische Beitrage zur Pathologic des 

Gehirns, Almquist and Wikoell, Stockholm, 1920-1922. 
S3. NIELSEN, J. M.: Agnosia, Apraxia, Aphasia, Hoeber, New York, 1945. 

34. KLEIST, K.: Gehirnpathologie vornehmhch auf Grund der Kriegserfahrungen, 

Johann Ambrosius Barth, Leipzig, 1934. 

35. BRICKNER, R. M.: The Intellectual Function of the Frontal Lobes; a Study 

Based upon Observation of a Man after Partial Bilateral Frontal Lobectomy. 
Macmillan, New York, 1936. 

36. FREEMAN, W. and WATTS, J. W.: Behavior and the frontal lobes, Trans. New 

York Acad. Sci., 1944, VI, 284. 

37. MILL, J. S.: Harvard Classics, Vol. 26, Collier, New York. 

38. BASTIAN, H. C: The Brain as an Organ of Mind, D. Appleton and Co., New 

York, 1880. 
Vol. VI. 1245 



BIBLIOGRAPHY 46 (6-7) 

39. PAVLOV, I. P.: Lectures on Conditioned Reflexes, Translated by W. Horsley Gantt, 

International Publishers, New York, 1928. 

40. BERGER, H.: Uber das Elektrenkephalogram des Menschen, Arch. f. Psychiat., 

XCIV, 16, 1931 ; a whole series of articles followed in various journals. 

December i, 1945. 



Vol. VI. 1245 



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divisions. In the sympathetic, each nerve cell (5) has an adrenal secretory cell {A) in con- 
nection with it. {Courtesy oj Edward Arnold. Publisher) 



48 



CHAPTER I-A 
ELECTROENCEPHALOGRAPHY 

By WILLIAM G. LENNOX 

Table of Contents 

Normal Electroencephalograms 46 (7) 

Modifying Factors of Brain Waves 46 (8) 

Constitutional Factors 46 (8) 

Environmental Factors • . 46(8) 

Physiological Alterations 46(9) 

Chemical Changes 46 (9) 

Chronic or Long Range Alterations 46 (10) 

Abnormal Electroencephalograms 46 (10) 

Patho-physiology 46 (12) 

Cortical Localizations 46(13) 

Mental States 46 (14) 

The Future of Electroencephalography 46 (14) 

Bibliography 46(14) 

Normal Electroencephalograms 

That the brain possesses electrical activity has been known since 1874. 
To Hans Berger of Jena and the year 1929 belongs the credit of demon- 
strating that these potentials could be led ofif through the intact human 
skull and recorded. Amplifying devices, developed in radio research, 
permit the "building up" of minute voltages which can then be made to 
trace a curve on film or on paper, either photographic or plain. Ink 
records on paper are used for clinical work for reasons of economy. For 
the patient the examination is simplicity itself. Electrodes are pasted 
to the scalp and the patient sits or lies quietly with eyes closed for fifteen 
minutes, while his brain busily scribbles an account of its activity. The 
potentialities of this technique for a better understanding of the activity 
of the brain in man and animals are great. Its value to the clinician is 
limited by various factors; the initial cost of the apparatus and the un- 
satisfactory performance of certain types, the need for expert care in 
maintenance and for competent interpretation of records after they are 
made. The technique of electroencephalography, reproductions of a great 

COPYJUGHT 1943 BV THE OXFORD UNA'ERSITY PRESS, NEW YORK, INC. 

46 (7) 



46 (8) ELECTROENCEPHALOGRAPHY 

variety of records and a bibliography of references are given in the 
Atlas of Electroencephalography, by Dr. and Mrs. F. A. Gibbs. Jasper 
has written an excellent review from a neurosurgical laboratory. 

In normal persons, who are awake, the brain waves, as they are popu- 
larly called, form a wavy line with fluctuations which recur from eight 
and one-half to twelve times per second and have a voltage from peak to 
trough of from ten to fifty millionths of a volt, microvolts. These weaves 
represent the discharge of nuclei of neurons. The configuration of the 
waves differs for difi^erent areas of the cortex and varies with the varying 
activity of the brain. The most easily identified and constant of the 
rhythms is obtained from over the occipital area when the subject's eyes 
are closed. This is called the alpha, or Berger, rhythm. Waves with a 
frequency of from one to sixty cycles per second may be encountered in 
the record. Wry fast rhythms have been called beta and very slow ones, 
delta, but statement of the actual observed frequencies per second is 
more accurate and, therefore, preferable. Both the frequency and the 
voltage of waves are important. 

Modifying Factors of Brain Waves 

In the human subject the brain waves may be modified by a number 
of conditions. An understanding of these is essential for the interpreta- 
tion of records. 

Constitutional Factors. — Study of the records of twins indicates that 
the pattern traced by the electrical waves of the cortex is an hereditary 
trait. In the examination of 65 twins Lennox, Gibbs and Gibbs found 
that identical twins without history of brain injury have brain waves 
which are indistinguishable, whereas the brain waves of non-identical 
twins differ. This fact is of importance in the study of the genetics of 
brain waves, particularly in conditions associated with unusual rhythms 
such as epilepsy. In a group of 320 near relatives of epileptic patients, 
52 per cent, had brain waves with some degree of abnormality, and in 95 
families, in which both parents were tested, the records of both parents 
were abnormal in 27 per cent., one was abnormal in 54 per cent., and 
neither was definitely abnormal in 19 per cent. 

Environmental Factors. — Decision as to whether a person's cortical 
dysrhythmia was transmitted or acquired may be difficult, unless brain 
wave records can be made of both parents, and a clcarcut history re- 
garding brain injury, either positive or negative, can be obtained. The 
etiology of dysrhythmia is indicated most clearly in the case of identical 
twins. If the records of these twins are unlike, the conclusion seems 

Vol. VI. 343 



NORMAL ELECTROENCEPHALOGRAMS 46 (9) 

justified that the difference is due to some environmental influence. En- 
vironmental conditions, which alter brain waves, may be physiological or 
pathological. 

Physiological Alterations. — Acute changes of brain waves attend 
alterations in the activity of the brain. The standard or basal conditions 
for making a record require the person to be awake, his eyes closed and 
his mind and body relaxed. Opening the eyes or "visualizing" with the 
eyes closed immediately causes increased frequency and decreased voltage 
of waves from the occipital areas, so that the wave frequency is counted 
with more difficulty. Apparently the increased activity of the optical 
tract imposes a faster frequency and interferes with the normal resting 
synchrony of the occipital area. To a lesser degree voluntary attention or 
sensory stimuli, which engage the attention, increase frequency and lower 
voltage. The onset of sleep is marked by faster, lower waves and deep 
sleep by large three or four per second waves which, if they occurred 
with the subject awake, would be pronounced grossly abnormal. Brain 
waves during involuntary sleep, as from drugs or narcolepsy, are similar 
to those of voluntary sleep. Hypnosis resembles the waking rather than 
the sleeping state. Attempts to correlate wave changes with thought or 
mood changes have not been rewarding. Loss of consciousness from any 
cause is accompanied by brain rhythm which would be abnormal were the 
person conscious. Maximum fatigue may be accompanied by abnormally 
slow waves. 

Chemical Changes. — Alterations of brain waves, which attend acute 
changes in the brain activity, such as attention, may be induced chemi- 
cally, a result of increased metabolic activity of the discharging cells. 
In animals a correlation between the oxygen tension of the brain and the 
frequency of its electrical pulsations has been demonstrated. In human 
subjects the relationship between the metabolism of the brain and brain 
waves has been studied by E. L. Gibbs and associates by means of the 
analysis of blood drawn simultaneously from an artery and an internal 
jugular vein while the subject's brain waves were being recorded. Of the 
substances which have been measured, the electrical activity of the brain 
is most readily influenced by changes in the carbon dioxide tension and 
the pH. Decreased concentration of carbon dioxide, of oxygen, of glu- 
cose and an increased alkalinity of the blood passing through the brain 
causes a slowing of the brain waves and an increase of certain types of 
abnormal waves. The opposite conditions cause a quickening of waves 
and an improvement of certain wave disorders. Drugs, which are con- 
vulsive or cause sleep, have a profound effect on the brain waves; smaller 
changes have been noted for various other types of drugs. 
Vol. VI. 343 



46 (lo) ELECTROENCEPHALOGRAPHY 

Chronic or Long Range Alterations. — Chronic, or long range, altera- 
tions of wave frequencies accompany growth and physiological cycles. In 
the newborn child waves are but one-half to two per second with voltages 
of from 20 to 50 microvolts with superimposed very fast, low voltage 
waves. The underlying rhythm gradually increases in frequency until 
by about the ninth year the record from the occipital area approximates 
that of the adult, although other areas remain relatively slow. The low 
voltage, fast record, encountered in 12 per cent, of normal adults, is sel- 
dom seen before the fourteenth year. By the nineteenth year records 
are fully adult. The aged tend to have either abnormally fast or slow 
waves. Paradoxically, dysrhythmia occurs less frequently in elderly than 
in youthful epileptics, although this may represent the survival of the 
rhythmic. Probably slight differences mark the sexes, and slight changes 
accompany the menstrual cycle. Waves become faster or slower with 
respectively increased or decreased basal metabolic rates and with in- 
creased or decreased body temperature. 

Abnormal Electroencephalograms 

The physician is most interested in the concurrence of abnormal 
waves and abnormal physical or mental behavior. These two groups do 
not exactly coincide, for a few normal persons have abnormal brain waves, 
and many abnormally behaving persons have normal waves. The degree 
of coincidence and the significance of various kinds of wave patterns can 
be judged by comparing the records of a sample of the population with 
the records of large groups of persons suffering from certain disorders of 
the central nervous system. 

The Gibbs have classified the records of 1,260 epileptics and of 1,000 
adult "controls", placing each record in one of eighteen groups. Samples 
of these eighteen tracings are shown in Fig. i, together with their 
percentage distribution in the control group. Of the 1,000 records, 84.4 
per cent, have waves which are fast but of such low voltage that they 
cannot be counted or else have a dominant frequency between 8.5 and 
12 per second. These are classed as normal. The waves of 13.8 per 
cent, are somewhat faster or slower, and of i.i per cent, are much faster 
or slower than the limits specified. In 0.9 per cent, the records contain 
occasional paroxysmal discharges of high voltage waves (marked "petit 
mal" and "psychomotor" in Fig. i). These are called "seizure dis- 
charges" because they resemble the tracings recorded during the various 
kinds of epileptic seizures. The types of abnormal records do not have 
equal pathological significance. In a group of 730 adult epileptics records 

Vol. VI. 343 



ABNORMAL ELECTROENCEPHALOGRAMS 46(11) 

E.E.G. CLASSIFICATION (GIBBS) 

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Fig. I. Classification of electroencephalograms used by the Gibbs. Electroencephalo- 
grams are placed by them in i8 classes; 15 of these were encountered in 1,000 "control" 
adults, their per cent, occurrence being indicated by the figures at the right of the tracings; 
three, the first and last two, marked at right 0.0 7c, are abnormal tracings, not encountered 
in the 1,000 "control" adults. These with 6 other tracings, making up 15.6 per cent, of the 
total encountered in the 1,000 "control" adults, are considered abnormal. In Fig. i then 
the five upper and the four lower tracings are considered as abnormal, the other nine as 
normal. At the bottom of the right hand corner is the signal, marked UV, made by 50 
micro-volts and the time interval of one second. Fig. i is from Gibbs, F. A., Gibbs, E. L., 
and Lennox, W. G.: Arch. Neurol, and Psychiat., article now in press. 

Vol. VI. 343 



46 (1 2) ELECTROENCEPHALOGRAPHY 

with paroxysmal discharges of high voltage waves occurred 34 times more 
frequently, very slow or very fast waves 17 times more frequently and 
slightly slow or fast waves only 2 times more frequently than in the 
control group. Further description of the electroencephalographic findings 
in epilepsy appear under that heading (see Oxford Medicine, Vol. VI, 
Chapt. XXX). 

Patho-physiology 

Disorders of the electrical pulsation of the brain may occur with or 
without demonstrable pathology or structural alterations of the brain. 
Abnormal pulsations probably represent some abnormality in the chemical 
makeup or reactions of the neurones of the brain or else some disturbance 
in the integration of nerve cell activity. The fact that brain waves are 
altered so easily by changes in the chemistry of the blood flowing through 
the brain speaks for a direct chemical action. As has been intimated, 
this abnormal state or reaction may be an inborn characteristic, the prod- 
uct of a certain gene molecule, or it may be an acquired characteristic, 
the result of environmental, chemical or structural changes. Genetic 
(essential) epilepsy is the clearest example of an hereditary cerebral 
dysrhythmia. Distinction between dysrhythmia which is based on 
metabolic or on organic disorders of the brain, is not always possible. 

In the metabolic group probably belong the bradyrhythmia of myxe- 
dema and the dysrhythmia of diabetes, of thiamine deficiency and of 
Addison's disease. These and other acute medical conditions have been 
studied insufficiently. Of especial interest are those in which loss of con- 
sciousness or convulsions may be a symptom. Psychoneurosis and hysterical 
seizures are not associated with disturbances of brain waves, although an 
hysterical person, like a normal person, may have dysrhythmia. Loss of 
consciousness from cerebral anemia, as in syncope and in the non-cerebral 
type of the carotid sinus reaction, are accompanied by slow, high voltage 
waves. The eclampsia, which occurs in certain cases of toxemia of 
pregnancy, may be due to a pre-existing dysrhythmia. Fever causes an 
increased speed of brain waves. In spite of its genetic linkage with epi- 
lepsy, the seizures of migraine are not accompanied by electrical brain 
storms, perhaps because the commotion is in the sympathetic nervous 
system. However, some degree of abnormality is at least twice as frequent 
in migraine patients as in the control group. The same statement can be 
made of persons with some aberration of behavior, inmates of prisons or 
behavior problem children. The distribution of wave patterns among 
persons of genius or of distinction needs to be ascertained. 

Vol. VI. 343 



ABNORMAL ELECTROENCEPHALOGRAMS 46(13) 

Besides the acute changes in body physiology, which have been 
mentioned, the brain may suffer direct injury with an accompanying dis- 
turbance of brain waves which may be reversible or irreversible. In the 
treatment of schizophrenia the administration of a convulsant drug or 
electric shock produces abnormal wave patterns which tend to subside in 
the course of weeks or months. The same may be said of infections 
which involve the cerebrum, brain abscess or edema, encephalitis, Syden- 
ham's chorea and meningitis. Trauma of the brain, tumors, foreign bodies 
and subdural hematomas produce localized disturbances, which tend to 
persist as long as the pathology remains or perhaps even spread and 
become generalized in persons who later will develop convulsions. It 
must be remembered that subcortical lesions, as in Parkinson's disease, 
mid-brain hemorrhages or lesions involving the cerebellum, may not be 
accompanied by demonstrable disorder of the electroencephalogram as 
ordinarily taken. Electroencephalography is intriguing because of its 
negative as well as its positive testimony. Sections of the brain may be 
amputated or extensive subcortical injuries may take place and the 
electroencephalographer be none the wiser. 

Cortical Localizations 

For ordinary diagnostic purposes a monopolar arrangement is used, 
one electrode on the head, the other on the lobe of the ear. The curve 
obtained represents the fluctuating electrical activity of the cortex in the 
region of the head electrode. With an apparatus, which writes six simul- 
taneous curves, an experienced person may detect a focus of abnormal 
discharge by noting the appearance of high voltage waves consistently in 
one or more of the curves. 

A technique of localizing cortical lesions was used first by Walter. 
In this method both electrodes, bipolar leads, are placed on the head. 
If the waves between these electrodes are the reverse of the waves be- 
tween two adjacent electrodes, an out of phase relationship, the lesion 
or its periphery lies between the two pairs. In practice sixteen place- 
ments of electrodes are used, and various adjacent regions are compared. 
In order to gain information about abnormal discharges in regions other 
than the cortex, electrodes have been placed in the nasopharynx, in the 
cisterna magnum and in the brain itself. Used in conjunction with neu- 
rological ex-aminations and pneumoencephalograms, electroencephalography 
is a great aid to the neurosurgeon. Of further aid to him is the classifica- 
tion of records used by Jasper. This author also pointed out the signifi- 
cance of diphasic spikes in areas of organic lesions. 

Vol. VI. 343 



46 (i4) ELECTROENCEPHALOGRAPHY 

Mental States 

Because of the importance of the mind in relation to brain activity 
the lack of dramatic correlations between mentality and brain waves is 
nonplusing. Encephalograms of the higher animals are as "good" as 
those of humans. There seems to be no correlation between intelligence 
quotients and the electroencephalogram. The feebleminded usually have 
normal records; on the other hand, those of deteriorated epileptics are 
grossly slow. The majority of patients with general paresis have abnormal 
records, the proportion being higher in those with seizures. The mental 
decay, which attends Schilder's disease and chronic encephalopathies of 
the aged, is associated with much dysrhythmia. 

In the case of the major psychoses the testimony is mixed. In manic 
depressive psychosis the evidence is indecisive. In schizophrenia ab- 
normalities occur several times more frequently than in control groups, 
but they are not concentrated in one type of pattern. 

The Future of Electroencephalography 

Fundamental experimental work on the pathway of nervous discharges 
and on the relationship between the metabolic and the electrical activity 
of the brain is now possible. A wide survey must be undertaken of the 
brain wave patterns in many samples of the population, both normal and 
abnormal but especially in persons with a disturbance of nerve function, 
of mentality or of behavior. Most intriguing is the possibility of pre- 
vention by means of eugenics of those mental and neurological diseases 
which are associated with an hereditary cerebral dysrhythmia. 

BIBLIOGRAPHY 

BERGER, H.: Ueber das Electrenkephalogramm des Menschen, Arch. Psychiat., 

1929, LXXXVII, 529. 
GIBBS, F. A. and GIBBS, E. L.: Atlas of Electroencephalography, A. Cummings, 

Cambridge, Mass., 1941. 
GIBBS, F. A., GIBBS, E. L. and LENNOX, W. G.: Electroencephalographic 

classification of epileptics and controls. Arch. Neurol, and Psychiat., in 

press. 
JASPER, H. A.: Electroencephalography, Chapter XIV in Epilepsy and Cerebral 

Localization b>' Penfield, \V. and Erickson, T. C, Charles C. Thomas, 

Springfield, 111., 1941. 
March i, 1943. 

Vol. VI. 343 



CHAPTER II 
VASCULAR DISTURBANCES 

B.Y E. FARQUHAR BUZZARD 

Table of Contents 

General Considerations 47 

Anatomical 47 

Physiological 4^ 

Cerebral Hyperemia 49 

Cerebral Anemia 49 

Lesions of Cerebral Vessels 5^ 

Etiology 50 

Thrombosis 50 

Embolism 5 1 

Hemorrhage 51 

Morbid Anatomy 52 

Cerebral Softening 52 

Hemorrhage 56 

Symptomatology of Vascular Hemiplegia 58 

The Signs of Hemiplegia 61 

Crossed Hemiplegia 6,^ 

Double Hemiplegia 63 

Trophic Disturbances 63 

Involuntary Movements 64 

Pain in Hemiplegia 64 

Diagnosis of Vascular Hemiplegia 64 

Prognosis 65 

Treatment 66 

Cerebral Hemorrhage 66 

Cerebral Thrombosis 67 

Hemiplegia 67 



General Considerations 

Anatomical. — Arterial blood is supplied to the contents of the skull 
mainly by the two vertebral and the two internal carotid arteries. These 
four vessels combine to form a large arterial plexus at the base of the brain, 
generally known as the circle of Willis, from which branches are distributed 
to the whole of both hemispheres. The vertebral arteries and the basilar 
artery, formed by their union, are mainly responsible for the blood supply 



48 VASCULAR DISTURBANCES 

of the pons, medulla and cerebellum. They take a part in the distribution 
of blood to the hemispheres through the posterior cerebral arteries, which 
also receive a contribution from the carotid system through the posterior 
communicating arteries. From the circle of Willis arise two groups of 
vessels: (a) a number of branches leaving the main trunks at a right angle 
and penetrating the substance of the brain to reach important central 
structures such as the basal ganglia and the internal capsules, and (b) a 
number of vessels which spread themselves over the surface of the hemi- 
spheres, breaking up into smaller and smaller branches in the meshes of the 
pia and sending countless offshoots into the cortex. Some of the latter 
terminate in the gray matter; others are of greater length and penetrate 
the white matter of the centrum ovale to reach the basal ganglia. In this 
way the territories supplied by each group incline to overlap, but there seems 
to be no real anastomosis between the two sets of vessels. 

The anterior, middle and posterior cerebral arteries, the three important 
arterial trees springing from the circle of Willis, are responsible for the blood 
supply of the cortex. Although their areas of distribution are more or less 
defined there is some overlapping and some anastomosis between small twigs 
belonging to adjacent branches of different parentage. 

From deep seated capillaries the blood is returned by small veins to a 
venous plexus on the surface of the brain. This plexus empties itself through 
the agency of larger vessels into the venous sinuses which lie in folds of the 
dura mater and which have intimate connections with each other. The la"ge 
venous lake formed by the sinuses is drained almost entirely by the two 
internal jugular veins, but there exist numerous, though small, channels of 
communication with the veins on the outer side of the skull. Of these 
channels the veins of the orbit and those of the diploe are the most impor- 
tant. In this way does intracranial venous congestion become portrayed in 
the face. 

Physiological. — ^The physiological principles which govern the cerebral 
circulation are still so imperfectly determined that the interpretation of 
pathological disturbances can only be a matter of surmise. According to 
modern teaching the cerebral circulation is controlled by the same influences 
as the circulation in other parts of the body. Thus the brain dilates with 
each cardiac beat and its blood content varies slightly with respiration. 
During inspiration blood is sucked into the thoracic cavity and during 
expiration the venous outflow from the skull is impeded. But the total 
amount of blood within the skull can vary but little inasmuch as the only 
other variable intracranial content, the cerebrospinal fluid, has but a small 
volume. The variations which take place are in the relative amounts of 
arterial and venous blood, an increase in one being associated with a cor- 
responding decrease in the other. The venous sinuses share in a general 



CEREBRAL ANEMIA 49 

venous congestion which affects the whole body such as that which follows 
prolonged expiratory efforts. On the other hand, the brain shares in the 
general arterial hyperemia associated with a rise in the blood pressure. 

The existence of a vasomotor mechanism controlling the cerebral circula- 
tion, independent of the general circulation, has long been a matter of dispute 
and the justification for regarding certain clinical phenomena as the result 
of a local vasomotor constriction or dilatation must depend on the final 
answer to this question. The facts that the cerebral arteries have muscular 
coats supplied by nerve fibers, that stimulation of the cervical sympathetic 
produces vascular changes in the brain and that certain drugs, such as 
adrenalin, can produce local results, support the view that the cerebral 
circulation may be regulated to some extent by a vasomotor mechanism of 
its own. 

Cerebral Hyperemia 

Although a large increase in the volume of blood in the cerebral vessels 
is not possible, an arterial hyperemia is recognized as a natural sequel to 
an increase of the general blood pressure. More arterial blood than usual 
passes through the brain in a given time and, unless this is associated with 
some morbid process such as the presence of a tumor or grave arterial 
disease, the results are physiological rather than pathological. Mental 
activity is increased and a sense of well-being may be experienced. On 
the other hand, a rise in blood pressure in the presence of increased intra- 
cranial pressure resulting from cerebral tumor, hydrocephalus, uremia or 
cerebral hemorrhage may bring about distressing and even dangerous 
symptoms in the fr>rm of headache, slowing of respiration and disturbances 
of consciousness. 

A venous hyperemia is the result of impeded outflow from the venous 
sinuses and in mild degrees may not give rise to symptoms. If continued 
for any length of time the brain must suffer from the corresponding decrease 
of arterial blood and the picture presented is that of cerebral anemia, with 
giddiness, faintness, clouding of consciousness and possibly convulsions. 



Cerebral Anemia 

This may be general or local. The results of general anemia are very 
similar whether they are produced by a diminution of the arterial supply 
or by venous congestion as described above. A diminished supply of 
arterial blood may be brought about by cardiac failure, by bleeding or by 
determination of the blood to the abdomen such as follows the rapid removal 
Vol. VI. 4 



50 VASCULAR DISTURBANCES 

of a large quantity of ascitic fluid. When cerebral anemia is rapidly or 
suddenly produced, loss of consciousness is the primary consequence and 
this may be followed by convulsions, slowing of pulse and respiration, 
dilatation of the pupils and rise of blood pressure. A continued state of 
anemia leads to an increase in the pulse rate associated with a fall of pressure 
and failure of respiration. 

The pathological changes associated with anemia have been studied in 
animals. A dog may survive the simultaneous ligation of both carotid and 
both vertebral arteries, but it presents a condition of idiocy and examination 
of the cortex reveals definite changes in the nerve cells. They become 
swollen, stain diffusely with methylene blue and lose their Nissl granules. A 
monkey does not survive a similar operation and in man the ligation of one 
carotid artery is not always a safe operation. Cerebral anemia, brought 
about gradually, also leads to definite changes in the nervous elements of 
the brain as is seen in cases of progressive double hemiplegia, the result of 
widespread cerebral arteriosclerosis. In such cases the cortical cells become 
atrophied and the nerve tracts degenerate. 

Local anemia of the brain frequently occurs as a sequel to arterial throm- 
bosis or embolism and the consequences will be described later. In order 
to explain certain clinical phenomena in the form of transient hemiplegias, 
monoplegias or hemianopias the possibility of a local anemia following local 
vasoconstriction has been entertained, but no confirmation of this hypothesis 
is yet available. 

Lesions of Cerebral Vessels 

Etiology 

Thrombosis.— The formation of a thrombus within the lumen of a cere- 
bral artery probably never occurs except as the result of embolus or of 
disease of the vessel wall. The etiology of embolism will be considered later. 

The arterial disease may be acute, subacute or chronic. Acute arteritis 
is the result of some infective process which may be limited to the vessel or 
which may involve the surrounding tissues as well. Thus arteritis with 
thrombosis is a rare complication of some of the acute specific fevers such as 
enteric fever, scarlet fever, diphtheria and possibly pneumonia. On the other 
hand, encephalitis, of whatever origin, is a potent source of arteritis, espe- 
cially in connection with the smaller arteries and secondary thrombosis is a 
common result. This has been well demonstrated in fatal cases of lethargic 
encephalitis and it is probable that similar effects are produced by the 
encephalitis of infancy due to the virus of poliomyelitis. It is not unreason- 
able to suppose that an inflammatory thrombosis of this nature is partly 
responsible, at any rate, for many cases of infantile hemiplegia. 



LESIONS OF CEREBRAL VESSELS 



51 



'^■}. 



'i» 



Subacute arteritis is most frequently the result of syphilis and the 
gummatous changes in the arterial walls generally lead to thrombosis 
(Fig. i). The middle cerebral artery and its branches appear to be peculiarly 
liable to this process, but the branches of the basilar artery and of the other 
cerebral arteries are by no means immune. A tuberculous meningo-arteritis 
is sometimes responsible for thrombosis of one of the cerebral arteries. 

Chronic arteritis or atheroma is the most common etiological factor in 
the production of thrombosis, especially when it is accompanied by an in- 
crease in the coagulability of the blood 
or by a fall of the blood pressure. The 
middle cerebral artery is again more 
prone to be involved in lesions of this 
kind. 

The acute infective forms of arteritis 
are more frequent in young persons, while 
atheroma is rare before fifty years of age. 
Between twenty and forty years of age 
cerebral thrombosis is nearly always the 
result of gummatous arteritis. 

Venous thrombosis is a comparatively 
rare occurrence and is usually a part of 
an acute infective process or, more rarely, 
associated with abnormal blood states 
such as chlorosis. 

Embolism. — An embolus in the cere- 
bral circulation may be a mass of fibrin, 
a piece of diseased cardiac valve, or pos- 
sibly a detached portion of the intima of 
the aorta or of its main branches. It 
brings about an arrest of circulation and 
thrombosis by becoming lodged at an 
arterial bifurcation, most frequently in the branches of the middle cerebral 
artery on the left side of the brain. 

Cerebral embolism is a circulatory accident which commonly occurs in 
young adults who are suffering from mitral stenosis. In cases of infective 
endocarditis the embolus may be the carrier of organisms to the brain and 
the infarcted area may become infected with the result that an abscess is 
formed. 

Hemorrhage. — The rupture of an artery is a much more frequent source 
of intracranial hemorrhage than the rupture of a vein, an extravasation of 
venous blood being almost always the result of some kind of injury. The 
essential condition of arterial hemorrhage is disease or trauma of the vessel 



J 



Fig. I. — Section of middle cere- 
bral artery showing arteritis, throm- 
bosis and organization of the throm- 
bus, from a case of gummatous 
arteritis of both middle cerebral 
arteries. 



52 VASCULAR DISTURBANCES 

wall and it is a matter of some dispute as to whether a healthy artery ever 
ruptures except as the result of violence. The chief exciting cause of hemor- 
rhage is a rise in the arterial blood pressure with or without a coincident 
venous congestion. Cerebral hemorrhage is rare under forty years of age 
and becomes increasingly common after the prime of life is past. It is more 
frequent in men than in women. 

Arterial or venous extravasation may be the result of birth injuries and 
so play an important part in the production of congenital hemiplegias or of 
diplegias. In childhood hemorrhage is probably an accident occurring in the 
course of an encephalitis except when it follows an injury to the head. Possi- 
bly a few cases result from the excessive strain put upon the cerebral vessels 
in the course of whooping cough. Dunng a paroxysm of coughing venous 
pressure is raised by expiratory efforts and arterial pressure is increased by 
muscular exertion. 

Between thirty and forty years of age syphilitic arteritis may occasion- 
ally be responsible for cerebral hemorrhage, but the large majority of cases 
are due to trauma. Atheroma and arteriosclerosis associated with granular 
kidney and hypertrophy of the left ventricle of the heart are the conditions 
which we have come to regard as the natural concomitants of cerebral 
hemorrhage after forty years of age and a very large proportion of all cases 
present this picture. 

It is of interest to note that cardiovascular accidents are particularly 
liable to cause death or disablement in certain families owing to the early 
advent of degenerative changes in the cardiac valves, the coronary and cere- 
bral arteries and in the kidneys. Any condition which weakens the arterial 
wall favors hemorrhage in the presence of a high blood pressure and it is 
still uncertain as to how frequently the escape of blood occurs from an aneu- 
rysm. 

Investigations seem to show that miliary aneurysms or minute dilata- 
tions of the smaller arteries are present in a large proportion of cases of 
cerebral hemorrhage, and that these may be associated with larger, some- 
times dissecting, aneurysms from which the fatal extravasation has taken 
place. 

Morbid A natomy 

Cerebral Softening. — Encephalomalacia results in any part of the brain, 
the arterial blood supply of which has been obstructed either by thrombosis 
or embolism (Fig. 2). This ischemic softening is limited to the area supplied 
by the artery and resembles in most respects the infarcts of other organs 
produced by similar conditions. 

The changes produced by ischemia should be studied after the organ has 
been hardened as a whole since those of recent origin are liable to escape 



LESIONS OF CEREBRAL VESSELS 



53 



detection if the brain is cut up on the post-mortem table. They vary consid- 
erably with the age of the lesion. 

In recent cases the ischemic area is swollen by serous exudation and, if 
it reaches the surface, the convolutions involved are enlarged and flattened. 
The consistence is little altered at first, but within a few days the central 
parts may be reduced to the consistence of creamy milk which they resemble 






* JSr-<-4,^5_ 




yy 



Fig. 2. — Section of brain showing areas of softening in both hemispheres caused by 
gummatous arteritis of both middle cerebral arteries. 



also in color. The edges present a redder tint due to the escape of capillary 
blood into the softened tissue. 

At a later period the softened area shrinks, the convolutions assume the 
appearance of moist wash leather and it is impossible to peel the soft men- 
inges from their surface without tearing away portions of the disintegrated 
brain matter. When the destruction has not been complete the convolu- 
tions may retain much of their normal size, but their surface is somewhat 
hard and pitted, resembling that of beaten silver. On the other hand, when 



54 



VASCULAR DISTURBANCES 



large areas have undergone complete necrosis they are represented by cystic 
cavities containing clear or slightly turbid fluid (Fig. 3). These cysts, 
when they reach the surface and are covered by the pia-arachnoid, present 
the picture of porencephaly. 

In cases of advanced and general cerebral arteriosclerosis in which the 
whole brain has suffered severely from vascular malnutrition there may be 
seen not one area of ischemic necrosis, but a large number of "lacunar" 




Fig. 3. — A brain showing the various results of cerebral thrombosis. Note the poren- 
cephalic cavity, the atrophied convolutions and the pitted surface of other sclerosed convo- 
lutions. 



softenings, small fluid containing spaces with well-defined walls, scattered 
throughout the hemispheres (Fig. 4). This condition is associated clinically 
with progressive double hemiplegia. 

Sections taken from the ischemic area of a very recent case may be 
remarkable only for the coagulated blood contained in the distended blood 
vessels, but this is usually associated with some impairment of the reaction 
of the tissues to staining reagents. The nuclei arc paler than normal and 
the myelin fails to stain well by the Weigert-Pal method. Nerve cells 



LESIONS OF CEREBRAL VESSELS 



55 



quickly undergo degenerative changes and staining methods no longer 
bring out their characteristic appearances. 

Within a few days the microscopic picture is profoundly altered by the 
presence of large numbers of compound granular cells containing one or 
more nuclei and a protoplasm filled with fat droplets, the products of 
tissue degeneration. They are derived from the neuroglia or from 




Fig. 4.— Section of a brain with widespread atheroma of the arteries. Thrombosis of 
the posterior cerebral artery has destroyed much of the left occipital lobe. Small areas of 
softening are to be seen in the basal ganglia. 

fibroblasts and act as scavengers, carrying their burden to the lymph spaces 
surrounding the blood vessels. 

The more highly specialized nerve elements succumb more easily than 
the neuroglia. When necrosis is present the neuroglia is destroyed in the 
central parts of the softened area, but in the peripheral parts neurogliar 
reaction may be detected. This takes the form of an increase in the size 
of the cells, division and multiplication of their nuclei and a proliferation of 
their processes. These fibrils form a dense network which spreads inwards 
and more or less fills up the space left by the destruction of brain matter. 



56 



VASCITLAR DISTURBANCES 



In smaller patches of softening the neuroglia survives and by its proliferation 
forms a sclerotic scar tissue which to some extent maintains the shape and 
size of the affected area. The blood vessels and their adventitial sheaths 
present a greater resistance to the necrotic process. Some are involved in 
the general disintegration, but others remain as strands of connective tissue 
which take a share in the scar formation. Newly formed vessels and fibro- 




Fig. 5. — Section of a brain showing a hemorrhage in the lenticular region. 



blasts are found in the older lesions so that the margin of the necrosed area 
is often largely composed of young granulation tissue. 

Secondary degeneration of nervous paths is the natural consequence of 
ischemic softening and the distant cells of the destroyed axones undergo 
"degeneration en distance." In the case of internal capsular lesions the 
Betz cells of the motor cortex are found to be reduced in number and those 
which survive to have undergone chromolytic changes. 

Hemorrhage. — Hemorrhage from a diseased artery is more common 
inside the brain than on the surface and most frequent in the gray matter 
of the basal ganglia (Fig. 5). In this region are found the Icnticulo-optic 
and lenticulo-striate arteries, to one of which Charcot gave the name of 
"the artery of cerebral hemorrhage." 



LESIONS OF CEREBRAL VESSELS 



57 



Any cerebral artery may rupture and the consequent extravasation of 
blood may attain any size or shape. In severe cases the blood ploughs 
through the brain substance to reach the subarachnoid space or one of the 
ventricles. In the latter case it may fill one ventricle after another and 
reach the subarachnoid cistern in the posterior fossa of the skull and thence 
pass along the posterior surface of the spinal cord (Fig. 6). 




Fig. 6. — Hemorrhage into the subarachnoid space at the base of the brain and spreading 
down the surface of the spinal cord. 



In the case of small hemorrhages the blood pushes back the surrounding 
tissues and produces its interference with function by pressure and secondary 
edema rather than by actual destruction of nerve elements. 

On the post-mortem table the hemisphere which contains a large ex- 
travasation of blood is increased in volume and its convolutions are flat- 
tened and often anemic. In recent cases the hemorrhage is represented by 
a red clot which can be separated readily from the surrounding brain 
matter. The latter is broken and discolored while smaller capillary extravasa- 
tions are often to be seen in the neighborhood. An edematous swelling of 
the surrounding tissues can usually be detected. 

In somewhat older cases the clot is found to be shrunken and to be partly 



58 VASCULAR DISTURBANCES 

or altogether yellowish in color. At a still later stage the site of the hemor- 
rhage may be occupied by scar tissue or by a straw colored fluid. The adja- 
cent brain substance undergoes changes similar to those described as occur- 
ring around an area of necrosis, an attempt to form scar tissue on the part 
of the neuroglial and connective tissues. In fact it is often impossible 
to distinguish the remains of an old softening from those of an equally 
old hemorrhage in the brain of patients who hav^e survived one of these 
vascular accidents for a considerable period of time. Even under the 
microscope the changes are very similar, except that the center of the focus 
in the case of hemorrhage is occupied by coagulated blood and not 
by necrotic brain tissue. The clot produces the effects of a foreign body on 
the surrounding structures, rendering them anemic and edematous. The 
nerve cells undergo regressive changes, the axones become swollen and 
varicose and the myelin sheaths break up into fatty droplets. Compound 
granular cells rapidly make their appearance and carry on the scavenging 
work for which they are destined. Ultimately the altered clot is invaded by 
spindle shaped cells with large vesicular nuclei and by new blood vessels, 
forming a granulation tissue which tends, with more or less success dependent 
on the original size of the hemorrhage, to obliterate the defect in the structure 
of the brain. Secondary degeneration of the nervous tracts involved in the 
hemorrhage may be traced by means of the Marchi or Weigert-Pal methods 
of staining. 



Symptomatology of Vascular Hemipleglv 

Hemiplegia, or paralysis of one side of the body, is only one of the many 
disturbances of function which can be and are produced by vascular acci- 
dents in the brain. It is the frequency with which the middle cerebral artery, 
and particularly those branches which supply the internal capsule and sur- 
rounding structures, is involved, which makes a stroke, or apoplexy, of 
such common occurrence as to deserve separate consideration. 

Hemiplegia is a symptom, not a disease and the clinical features by which 
it is characterized are the same whether the lesion responsible for it is vas- 
cular, inflammatory, neoplastic or degenerative. The vascular hemiplegias, 
moreover, are the same whether they result from softening or from hemor- 
rhage and the only part of the clinical picture which may present diff'erences 
is the mode of onset. Before discussing the various modes of onset it may be 
as well to state that in a large number of cases it is difficult to determine 
whether the lesion is in the nature of a thrombosis or a hemorrhage, although 
it is quite clear that the condition is of vascular origin. This should not 
cause much surprise in view of the fact that the conditions favoring throm- 



SYMPTOMATOLOGY OF VASCULAR HEMIPLEGIA 59 

bosis and hemorrhage are in many respects similar, at any rate as far as the 
presence of arterial disease is common to both. 

In discussing the etiology we have observed that arterial disease is 
present in most cases of cerebral hemorrhage and cerebral thrombosis, the 
other factor of importance being the condition of the blood pressure. In 
any particular case of apoplexy seen by a medical man within a few hours of 
onset it may be very difficult to determine whether the blood pressure was 
high or low when the stroke occurred and a decision on this point may be 
arrived at only from circumstantial evidence. The shock produced by a 
severe hemorrhage may be associated with a temporary but considerable 
fall of blood pressure and the medical attendant may thus be deceived when 
he sees the patient at that stage. 

When a hemiplegia develops slowly in the course of a few hours, perhaps 
with remissions and relapses, the diagnosis may again be a matter of some 
difficulty and the observer may have to decide whether the process is a 
slowly spreading thrombosis or a slow leakage of blood from a small vessel. 
We have already seen that in both cases the disturbance of function may be 
complicated by edema of the tissues in the neighborhood of the lesion. 

In a typical case of cerebral hemorrhage the onset may occur when the 
patient is enjoying the best of health or, if he has any premonitory symp- 
toms, they are those which are commonly associated with arteriosclerosis 
and a high blood pressure, such as occasional headaches and slight attacks 
of giddiness. The seizure is abrupt and the patient may fall unconscious 
while engaged in some active physical pursuit or when under the influence 
of some violent emotion. Death may be the immediate result, but in the 
majority of cases the patient lies in a state of profound unconsciousness 
with slow and stertorous breathing. The face is pale or slightly cyanosed 
and the skin is moist with sweat. The eyes are only partially closed, the 
pupils are contracted and react sluggishly to light. The conjunctival reflex 
is either abolished or much diminished especially on the paralyzed side. 
There is no reaction to painful stimuli, the limbs are flaccid and the sphinc- 
ters are relaxed. Occasionally at this stage there are convulsive movements 
affecting the face and limbs on the side opposite to the lesion and in the 
interval between these movements the eyes may be persistently directed 
towards the non-paralyzed side of the body. All reflex movements are 
temporarily abolished or greatly diminished in activity. 

For a time it may be difficult to determine on which side of the brain the 
hemorrhage has occurred and only a careful examination enables the observer 
to come to a decision on this point. The muscular tone, detected while 
making passive movements of the limbs, may be more completely lost on the 
hemiplegic side and the paralyzed side of the face may flap more obviously 
during respiration. Some degree of response to painful stimulation may be 



6o VASCULAR DISTURBANCES 

obtained on the non-paralyzed side and sometimes an extensor response is 
only obtained from the opposite foot. 

This condition of coma may persist for hours and even days and death 
may take place at any period. In non-fatal cases recovery from the comatose 
condition is gradual and is indicated in the first instance by signs of irrita- 
bility and resentment in answer to manipulations and examinations. Any 
pinching of the skin produces a defensive movement especially on the non- 
paralyzed side. The patient resents light thrown into his eyes and the 
conjunctival reflex returns on the side of the lesion. Within a few hours there 
is generally a slight rise of temperature which is more marked on the par- 
alyzed side. Ophthalmoscopic examination during the comatose stage may 
reveal no abnormalities, but in a considerable proportion of cases there is 
some edema of the discs which may be associated with retinal changes 
characteristic of renal disease. 

In other less severe cases of cerebral hemorrhage the patient may suffer 
from momentary loss of consciousness or from transient giddiness associated 
with loss of power in the limbs on one side. This condition of hemiplegia 
may pass away in a few hours or a few days, perhaps to return in a more 
severe form if the warning it provides has not been attended to. 

In cases of cerebral softening due to embolism the onset is always abrupt; 
it is often accompanied by loss of consciousness and sometimes by convul- 
sions. When the area of brain involved is a small one consciousness may be 
retained and the patient may only complain of pain in the head and giddiness 
or faintness while the hemiplegia develops. 

The symptoms of hemiplegia resulting from thrombosis of the cerebral 
arteries may be either abrupt or gradual in onset. In the former case they 
can hardly be distinguished from those of cerebral hemorrhage, and the 
diagnosis must depend upon any data which may be available in regard to 
the condition of the patient's health and blood pressure. More commonly 
thrombosis is manifested by a very insidious onset of hemiplegia. The 
patient on attempting to leave his bed in the morning finds that he is unable 
to stand, or he may be sitting quietly in a chair and finds that one or other 
hand has become weak or powerless. He may be quite free from any signs 
of discomfort in his head and is apt to regard the uselessness of an arm as the 
result of its having been rested in some unaccustomed position for an undue 
length of time. He may not realize that the leg on the same side is affected 
until he attempts to get up and move away. Not infrequently the loss of 
power passes off in the course of a few minutes only to return in a more 
permanent form some hours later. 

Another mode of onset is characterized by the slow development of 
hemiplegia followed by loss of consciousness and in many cases the patient 
is found in this condition in the morning after having gone to bed at night in 



SYMPTOMATOLOGY OF VASCULAR HEMIPLEGIA 6i 

apparently good health. Convulsive movements affecting the whole or 
part of the paralyzed side may recur from time to' time during the develop- 
ment of this condition. 

Premonitory symptoms of thrombosis take the form of transient sensa- 
tions of formication or numbness in one or other limb or, in the case of 
left sided lesions, of transient attacks of difficulty in speech or aphasia. 
These premonitions may recur from time to time over a period of weeks or 
even months, especially in old people with enfeebled hearts, and are indica- 
tive of transient ischemia in parts of the cerebral circulation. 

The Signs of Hemiplegia 

These are the result of a lesion of the corticospinal tract and differences 
depend only on the extent and not on the nature of the damage inflicted by 
the vascular accident. There are certain principles which should always be 
remembered in relation to the effects produced by unilateral interference 
with the functions of the pyramidal tract. In the first place, it should be 
realized that movements, not muscles, are affected. In the second place, 
the movements most affected are those which are naturally unilateral. In 
the third place, the more highly specialized movements, those which have 
been latest developed, are more affected than those which are completely, 
or nearly completely, automatic. In a hemiplegic patient, after the shock 
stage has passed away, the affected side of the face may exhibit little change 
at rest, although there may be differences in the lines of the face. Little 
asymmetry may be observed during strong emotional movements, but 
voluntary actions, such as that of showing the teeth, bring out the weakness 
on the affected side. Closure of the eyes may be well performed, but if 
resistance is offered the strength of the closure movement on the affected 
side can be demonstrated; moreover the patient is unable to close the eye 
on that side without closing the other at the same time. Movements of the 
forehead and eyebrows being largely bilateral are little affected. The func- 
tions of phonation, articulation, mastication and deglutition being largely 
automatic and bilateral are not interfered with to any extent and the tongue 
performs its ordinary movements with little difficulty. If the patient is 
asked to protrude his tongue it tends to deviate towards the side of the lesion. 

The movements carried out by the muscles of the neck and the trunk, 
which are largely concerned in the automatic maintenance of the erect 
position, are comparatively little affected compared with those of the limbs. 
Hughlings Jackson pointed out that in automatic respiration the movements 
of the affected side of the chest may be slightly greater than those of the 
opposite side, but when a forced respiratory effort is made the asymmetry 
is reversed. 



62 VASCULAR DISTURBANCES 

In the majority of cases of hemiplegia the arm is more affected than the 
leg and the movements of the fingers more affected than those at the shoul- 
der, elbow and wrist. After a preliminary stage of fiaccidity there is a 
tendency for the limb to adopt a definite posture, which is determined by 
involuntary adduction and internal rotation at the shoulder, flexion and 
pronation at the elbow and flexion of the wrist and fingers. The last move- 
ments to be regained are the finer and more specialized functions of the 
thumb and finger, and it is rarely that the patient who has sustained a severe 
attack of hemiplegia is able to carry out such delicate manipulations of the 
hand as are involved in playing instruments with his previous facility. 

The lower extremity assumes a position of extension with the foot in the 
position of equino-varus. Walking is made difficult by the toes catching 
the ground, and the patient learns to overcome this obstacle by circum- 
ducting the leg at the hip when he advances the limb. 

Associated with these limb postures is found an increase of tone or rigidity 
in the muscles which preponderate and any attempt to passively correct the 
postures is met by a certain amount of involuntary resistance. In the course 
of time the afi"ected muscles and tendons become contracted and the postures 
thus become permanent deformities. 

It is characteristic of hemiplegia that certain automatic acts are asso- 
ciated with involuntary movements. Thus a patient may be unable to 
extend his fingers and wrist voluntarily, but may perform those movements 
involiintarily while yawning. Another remarkable feature is the tendency 
for the paralyzed limbs to make movements in association with strong 
muscular movements carried out on the non-paralyzed side. 

All tendon jerks in the paralyzed limbs are increased and clonus may be 
elicited in certain situations, such as the knee and ankle, more rarely in the 
upper extremity. On the paralyzed side the abdominal and cremasteric 
reflexes are usually abolished except in young children and the plantar 
reflex, is altered in character. On stimulating the sole of the foot the big 
toe is extended instead of flexed. Disturbances of the sphincter reflexes do 
not as a rule persist for long after the initial stage, but the patient may 
complain of some precipitancy in connection with the bladder. 

The above description applies to the majority of cases of hemiplegia, 
but there are exceptions to the general rule in regard to the question of 
rigidity and posture. In some cases, for instance, the tone is not increased 
and the limbs may remain flaccid even when a certain amount of recovery of 
voluntary movement has been obtained. This is particularly the case when 
the motor loss is complicated by considerable disturbances of sensibility. 
In ordinary cases of hemiplegia the hemianesthesia, which may be present 
in the early stages, tends to disappear, at any rate as far as sensibility to 
painful and thermal stimuli is concerned. On the other hand, the sense of 



SYMPTOMATOLOGY OF VASCULAR HEMIPLEGIA 63 

passive position and passive movement is generally affected for a long time 
and in many cases permanently. 



Crossed Hemiplegia 

When a vascular lesion affects the corpus quadrigeminal region there may 
be found third nerve palsy on one side associated with paralysis of the face, 
arm and leg of the opposite side. Vascular lesions in the pons due to hemor- 
rhage or thrombosis of one of the branches of the basilar artery produce 
another form of crossed hemiplegia in which the face may be affected on one 
side and the arm and leg on the other side. Under these circumstances the 
facial palsy may show the characteristic features of a nuclear lesion. All 
the facial muscles may be involved and may undergo atrophy and the elec- 
trical reaction of degeneration. 

Double Hemiplegia 

This occurs as the result of vascular accidents either from a single lesion 
in the pons where the two pyramidal tracts are in close approximation, or 
from two separate lesions occurring at different times in the internal capsules 
of both hemispheres. The picture presented in either case is that to which 
the term pseudobulbar palsy has been given. In double hemiplegia we find 
not only all the signs associated with hemiplegia on both sides of the body, 
but in addition an interference with a number of other functions which 
escape when the lesion is unilateral. Thus articulation and deglutition be- 
come involved and the patient suffers from dysarthria and dysphagia. 
His powers of mastication may be seriously affected and his trunk move- 
ments may be so enfeebled as to add greatly to his general disability. In 
these cases, too, there is usually much impairment of sphincter control. 

Trophic Disturbances 

Bedsores are not a common complication of the hemiplegic state, but 
may occur in the early comatose stage following a cerebral hemorrhage or 
thrombosis unless very careful nursing is carried out. General loss of weight 
is likely to occur in the early stages, but may be followed by an increase due 
to the interference with activity. Atrophy of muscles on the paralyzed side 
is usually inconspicuous but in certain cases it is remarkable even in the 
absence of arthritic changes. Secondary arthritis is common, especially in 
the shoulder joints, but depends very largely on the amount of attention and 
treatment which is given to the limbs while the patient is bedridden. 

Vasomotor disturbances are common and the affected limbs are usually 



64 VASCULAR DISTURBANCES 

cyanotic and sometimes edematous especially in their peripheral parts. 
Sweating may l)e excessive, but the surface temperature is generally re- 
duced to the extent of several degrees as compared with the sound side. 



Involuntary Movements 

In a small proportion of cases of hemiplegia there is observed a variety 
of involuntary- movements. Sometimes there is a fine rhythmical tremor 
not unlike that of paralysis agitans. Other cases exhibit a tremor of the 
so-called intention type most marked at the termination of a purposive 
movement. Following the infantile hemiplegias athetotic and choreiform 
movements present a distressing complication, and once established they 
tend to persist indefinitely. 



Pain in Hemiplegia 

In the majority of cases of vascular hemiplegia pain is not a conspicuous 
symptom and when complained of can generally be referred to arthritis. 
This occurs w-hen the paralyzed limbs have been allow^ed to remain in fixed 
positions and passive movements have been neglected. There are, however, 
occasionally seen cases of hemiplegia associated with what is known as the 
thalamic syndrome. These patients present peculiar sensory disturbances. 
Their appreciation of painful and thermal stimuli is lowered but such stimuli, 
when sufificiently strong, produce intensely disagreeable results which are 
badly localized. In addition, these patients frequently complain of severe 
paroxysms of pain referred to the paralyzed limbs. 



Diagnosis of Vascular Hemiplegia 

The diagnosis of vascular hemiplegia can be conveniently divided into 
two parts: (i) The differentiation of apoplexy from other conditions giving 
rise to acute and profound loss of consciousness. (2) The diagnosis between 
cerebral hemorrhage, cerebral thrombosis and cerebral embolism. 

I. A state of apoplexy may be mistaken for an acute toxic condition 
such as is produced by alcohol, opium or diabetic coma. The presence, there- 
fore, of asymmetrical hemiplegic signs on careful investigation should pre- 
vent this mistake being made. An alcoholic odor should not be deemed a 
strong point in favor of alcoholic poisoning as the taking of alcohol is a 
not infrequent precursor of hemorrhage. An early examination of the urine 
should always be made in these states and this should be sufficient for the 
detection of diabetes. The presence of albuminuria does not suffice to dis- 



PROGNOSIS 65 

tinguish between cases of cerebral hemorrhage and cases of uremia and it 
must be remembered (a) that a cerebral hemorrhage may precipitate the 
onset of uremic coma in a patient suffering from renal disease, (b) that a 
patient suffering from granular kidney is particularly prone to cerebral 
hemorrhage, and (c) that in uremia hemiplegic signs and symptoms are apt 
to arise even in the absence of a cerebral hemorrhage. 

Hemiplegia is a not uncommon result of encephalitis, but in these cases 
it is usually associated with or preceded by other symptoms in the form of 
headache, pyrexia, ocular palsies, etc. It should not be forgotten, however, 
that a cerebral hemorrhage may occur as a complication of encephalitis, and 
in some cases an examination of the cerebrospinal fluid may afford a clue to 
the diagnosis. Hemiplegia may be present in the congestive attacks of 
general paralysis of the insane, but is usually transitory and signs of syphilis 
can be detected. 

2. The diagnosis of cerebral embolism is dependent on the presence of 
some condition favoring the production of an embolus in the thoracic organs. 
It can hardly be made unless evidence of old or recent endocarditis is present. 
Cerebral hemorrhage can be presumed as the cause of hemiplegia in the case 
of a patient who has a high blood pressure, a full bounding pulse and a hyper- 
trophied left ventricle, but cannot be excluded within a few hours of the 
stroke if the blood pressure is then low and the heart's action rapid and feeble 
as the result of shock. Cerebral thrombosis is the usual cause of a hemi- 
plegia which develops slowly in the course of a few hours in elderly people 
with enfeebled circulation. On the other hand, there is little doubt that 
cerebral hemorrhage is sometimes a secondary result of cerebral softening 
and occurs in relation to a vessel which has lost the natural support afforded 
by healthy surrounding tissues. 

Speaking generally, there are many cases in which the diagnosis between 
thrombosis and hemorrhage is impossible, especially if It is attempted at a 
considerable distance of time after the stroke has occurred. 



Prognosis 

An attempt to prophesy what is going to take place in the case of a 
vascular hemiplegia is more or less a matter of guess-work. It is impossible 
to determine by any methods at our disposal whether the interference with 
the function of the pyramidal tract in the early stages is due to an actual 
destruction of the fibers, or to pressure and edema secondary to a lesion in 
their neighborhood. In the former case regeneration is impossible and the 
hemiplegia must, therefore, be permanent. In the latter case a complete 
recovery is not only possible but probable. In the majority of instances 
Vol. VI. 5 



66 VASCULAR DISTURBANCES 

there may be a combination of both factors at work so that the result is a 
partial recovery of function. Speaking generally, the less severe the initial 
lesion, the less prolonged the state of coma if such exists, the better the 
prognosis, but a primitive knowledge of the anatomical conditions makes it 
quite clear that even a small lesion may produce permanent results. It is 
generally safe to say that some recovery is likely to take place, but that time 
alone can show to what extent function can be regained. 



Treatment 

Cerebral Hemorrhage 

A patient suffering from apoplexy, or from any symptoms even suggestive 
of an approaching seizure, should be put to bed without delay and kept 
there. If there is reason to suppose that hemorrhage is occurring precautions 
should be taken to avoid all unnecessary movements and all mental and 
physical disturbances. 

The comatose patient should lie with his head and shoulders slightly 
raised and the face turned to one side in order to prevent the tongue falling 
back and so interfering with respiration. If a water-bed is available it 
should be used, but it is unwise to shift a patient during the first few hours 
for this purpose. The bladder should be emptied by means of a catheter 
and the patient kept clean and dry with scrupulous care. Starvation for 
twenty-four hours will probably be beneficial, but the patient's mouth 
should be kept clean by frequent sponging and the use of some antiseptic 
preparation such as boro-glyceride. The action of the bowels should be 
obtained as soon as possible by the administration of calomel or croton oil 
followed, if necessary, by an enema. 

In the case of patients with a high blood pressure and obvious signs of 
congestion the question of bleeding has to be considered. No dogmatic 
opinion can be given on the efficacy of this measure, but it may be assumed 
that no harm will result from the removal of lo to 20 ounces (300 to 600 c.c.) 
of blood by venesection. The number of cases in which bleeding can be 
stated with confidence to have saved the patient's life must be very small. 

Still more caution is required in considering the employment of surgical 
decompression as a therapeutical measure in these cases. When a patient's 
life is threatened by increased intracranial pressure it may be justifiable to 
perform a subtemporal decompression, both the bone and dura being freely 
opened. This operation is not without the risk of producing an increased 
amount of laceration of brain substance as the extravasated blood may burst 
through the convolutions on to the surface of the unsupported area of brain. 



TREATMENT 67 

In order to avoid this an attempt may be made to tap the clot and drain it 
through an artificial opening chosen by the operator. Ligation of the carotid 
artery on the side of the hemorrhage has been performed in a certain number 
of cases, but this operation is attended by the risk of causing widespread 
softening and can rarely be justified. 

When the acute stage has passed and the patient is recovering conscious- 
ness the chief symptom to be met is that of restlessness. A simple sedative 
like bromide, combined with complete quiet, may be a sufificient remedy, but 
morphia may be necessary and beneficial. Rest in bed for a few weeks with 
careful nursing and a low diet should be ordered in every case. 

Cerebral Thrombosis 

In the acute stage the patient should be kept absolutely still as in the 
case of cerebral hemorrhage. If the patient is suffering from a weak heart 
and a low blood pressure active purgation must be avoided and the bowels 
kept open by means of a mild aperient and enemata. Feeding either by the 
mouth or by the rectum should be commenced at an early stage, and stimu- 
lation by means of alcohol and digitalis may be indicated. If syphilis is 
suspected an intramuscular injection of mercury may be given at once and 
repeated at weekly intervals, or the same effects may be attained by means 
of daily inunctions. Potassium iodide, in increasing doses, should be ad- 
ministered by the mouth as soon as the patient is able to swallow. 

Hemiplegia 

It has already been pointed out that in all vascular accidents affecting 
the brain it is impossible to determine how far the symptoms are due to 
destruction of nerve tracts, and how far they are the result of edema and 
compression. This ignorance justifies the adoption of a hopeful attitude and 
necessitates the employment of every measure likely to facilitate recovery 
even in the most unpromising cases. 

Success in dealing with hemiplegia depends largely on an intelligent 
anticipation of the difficulties which are likely to be met with and on enlisting 
the patient's active cooperation in his treatment. 

Armed with the knowledge that the patient's paralyzed limbs will tend, 
if uninterfered with, to assume certain fixed positions, already described, it 
should be the object of the doctor and nurse to counteract this tendency from 
the beginning. Even during the comatose stage the nurse should see that 
the arm and leg, particularly the former, are never allowed to lie for long 
periods in one position. The upper arm should be kept away from the chest 
by an interposed pillow, the forearm should often be supinated and placed 



68 VASCULAR DISTURBANCES 

in the extended position, and the wrist and fingers may even be placed for a 
few hours at a time in some form of spHnt to oppose continued flexion. 
Passive moxements should be carried out at least two or three times daily 
at every joint and gentle massage applied to the muscles. 

As soon as the patient recovers consciousness and is sufficiently recovered 
mentally to appreciate his condition he should be educated up to the belief 
that he is going to take the chief part in his own treatment. He should be 
told that his arm and his leg are not the seats of his disease, that every volun- 
tary movement will require his own initiation, and that the manipulations 
of the nurse and the masseur aim only at keeping the limbs in good condition. 
It is equally important that the masseur should appreciate his own limita- 
tions and that he should encourage the patient to cooperate in all move- 
ments. The patient will naturally tend to practise and strengthen those 
movements which come first and most easily to him. He should be instructed 
not to neglect those he finds difficult or even those he cannot perform. It is 
a good plan to explain to him the different movements which are naturally 
performed at each joint and to ask him to spend a certain amount of time 
every day attempting each movement in turn even in the absence of any 
physical response. He should do the same thing while the masseur is carry- 
ing out passive movements, and the latter should engage his attention to 
this end. 

Only by such methods will the patient overcome the resistance offered 
to his recovery in the form of spasticity, contractures and deformities, and 
only by steady perseverance in them will he obtain the maximal amount of 
voluntary power which is possible in his case. Equally important is the 
avoidance of bad habits when the patient begins to get about. If left to 
himself the patient will walk with an extended leg which he circumducts 
and swings in order to prevent the toes catching the ground. He should be 
taught to persevere in advancing his leg by flexion at the hip and knee, and 
he should not be allowed to sit with his paralyzed leg adducted and his toes 
pointing inwards. 

It will be noticed that no mention has been made of electrical treatment 
in regard to these cases. Electricity has no place in the treatment of hemi- 
plegia and its daily application to the paralyzed limbs is a waste of time and 
money in the large majority of cases. It tends to make the patient believe 
that recovery is going to take place as the result of external applications and 
so minimizes the value of his own efforts which are all important. It can 
only be of use in rare cases in which certain muscles have undergone second- 
ary atrophy. 

The principles which should govern the treatment of hemiplegic patients 
having been grasped, the medical attendant will be able to apply them and 
modify them in relation to individual cases. 



CHAPTER II-A 

CEREBRAL ARTERIOSCLEROSIS WITH REPEATED THROM- 
BOSIS OF SMALL INTRACRANIAL ARTERIES 

By WALTER C. ALVAREZ 

Table of Contents 

Introduction 68 (i) 

Synonyms 68 (i) 

Definition 68 (i) 

History 68(2) 

Distribution and Occurrence 68 (3) 

Etiology 68 (4) 

Pathology 68 (4) 

Life History of the Disease 68 (4) 

Case Records of Little Strokes 68 (4) 

Symptoms 68(12) 

Common Manifestations of the Disease 68 (13) 

Diagnosis 68 (17) 

Prognosis 68 (19) 

Treatment 68 (20) 

Bibliography 68 (21) 

Introduction 

Synonyms. — Spasm of intracranial blood vessels, minor apoplexies, small 
strokes, vascular accidents. 

Definition. — Cerebral arteriosclerosis is a chronic disease of the small intra- 
cranial arteries which results in thrombosis here and there and the formation of 
many infarcts, most of them less than 5 mm. in diameter. With each infarct a 
small part of the brain is destroyed, and eventually enough is put out of action so 
that the victim becomes tired and weak, perhaps changed in character, and aged 
beyond his years. In the end the process results in death, perhaps 10, 15 or 20 
years after the first symptoms appear. 

As will be seen later, many of the infarcts are too small to produce any recog- 
nizable symptoms; larger ones may result in dizziness, a sense of great fatigue, a 
loss of the feeling of well being, loss of interests, loss of memory or a loss of ability 

COPYRIGHT 1947 BY THE OXFORD UNIVERSITY PRESS, NEW YORK, INC. 

68 (i) 



68 (2) CEREBRAL ARTERIOSCLEROSIS 

to work. Naturally the severity of the symptoms depends on the extent and 
number of the infarcts and their location in the brain. 

The patients commonly live on for years without becoming demented or 
childish or without the nature of their disease becoming apparent. Only occa- 
sionally will an infarct be large enough or so situated in the brain that the attend- 
ing physician can see clearly that an injury was wrought to the nervous system. 
Many a person with this disease has one or more episodes and then goes for years 
without another recognizable one. 

History 

A search through the literature so far has not revealed any good description 
of this common disease. A few outstanding clinicians like Janeway and Peabody 
mentioned it but, curiously, appeared to be reluctant to go ahead and describe 
it in detail. Because the manifestations of the malady are usually spread over 
lo or 20 years, and the several episodes are seen by different physicians, few 
internists have a chance to learn anything about the disease in its entirety. 
About the only way in which a physician can come to know this disease well from 
start to finish and with all its bizarre manifestations is to watch a parent or close 
relative or friend die slowly from it. For some strange reason the disease is sel- 
dom mentioned in books or journals; it practically never is discussed at medical 
meetings, and perhaps never is a case demonstrated before medical students in 
the college amphitheater. 

In books on arteriosclerosis, psychiatry, neurology or geriatrics one can find 
descriptions of the types of senile dementia, which can result from a severe 
apoplexy or a series of them, but one seldom finds descriptions of the type of mild 
episode described here, and nowhere has the writer found a detailed description 
of the long-lasting episodal disease dealt with in this article. 

One big reason for this is that physicians have a strong repugnance for mak- 
ing the diagnosis of a stroke. They fear to discourage and to offend or to cast a 
stigma on the patient and the family, and hence in these cases they usually diag- 
nose acute indigestion, or Meniere's disease, or a liver attack or a heart attack. 
In many cases it is only the patient and his family, who recognize the fact that 
there was a little stroke, or they have a good hunch that this is what happened. 
In all bad cases the wife and the family usually will realize that something 
terrible happened to the patient's brain; they see perhaps a big change in char- 
acter and personality, and often they have on their hands a changeling who is 
extremely difficult and tr}dng to take care of. Often he is worse than any prob- 
lem child. He is no longer the strong and efficient and friendly person he was 
before the cerebral accident. Often the family realizes that the wage earner is 
done for and will never work again, but curiously, they seldom mention these 
Vol. VI. 1 147 



DISTRIBUTION AND OCCURRENCE 68 (3) 

facts to the attending physicians. They talk only of the digestive disturb- 
ances. 

Oftentimes the family physician will promptly make the correct diagnosis 
because he knew the patient before the acute episode, and he can see the tremen- 
dous change that came suddenly at a certain minute of a certain day. He per- 
haps goes into the home and sees what a terrible problem is being faced by the 
family, and he may also hear from the man's business associates that at the office 
he is no longer of any use; he is no longer initiating anything, and he is perhaps 
so irritable and unreasonable that he is fighting with all his subordinates. 

The problem of diagnosis is much more difficult for the city consultant, be- 
cause he never saw the man before and hence does not know what sort of person 
he was. He seldom gets the story of the initial stroke; he seldom learns of the 
terrible problem in the patient's home, and he seldom hears about what is hap- 
pening at the man's place of business. As already noted, neither the patient nor 
the family mentions the really significant parts of the history, and hence if the 
consultant does not note signs of mental deterioration or get a hunch as to what 
happened, so that he thinks to ask the relatives about a sudden illness with a 
change in character and efficiency, he will miss the correct diagnosis. If, as is so 
customary today, he depends for his diagnosis on the results of laboratory tests 
and roentgenological studies of the digestive tract, he will be led astray because 
the tests will not help him. 

One sweet old lady summed up the situation very well when she said, "death 
is taking httle bites of me ". She saw that with each attack of dizziness or fainting 
or mental confusion she became a little older, a little weaker and a bit more tired; 
her step became more hesitant, her memory less trustworthy, her handwriting 
less legible and her interests in life less keen. She could see clearly that for 10 
years or more she had been moving step by step toward the grave. 

The only physician who saw this problem in its entirety appears to have 
been Osier who in his usual inimitable way spoke of the many men and women 
who " take as long to die as they did to grow up ", who go " through cold gradations 
of decay" and ''who live a sort of death in life". 

Distribution and Occurrence 

This disease probably begins most often in the fifties and sixties, but not 
infrequently it begins in the forties, and there is considerable evidence to indicate 
that in some persons it begins in the thirties. Naturally when a sudden dizzy 
spell followed by a nervous breakdown comes in the thirties or forties, it is hard 
to say if it was part of the disease which eventually killed the patient in the fifties 
or sixties, but there are many case histories which suggest strongly that this was 
the case. Every physician of experience knows that vascular accidents with 
Vol. VI. 1147 



68 (4) CEREBRAL ARTERIOSCLEROSIS 

typical hemiplegia can happen to young persons even in the second and third 
decades of life, and during the last war it was noted that quite a few young 
soldiers suffered a coronary thrombosis. 

It is probable that thrombosis of small intracranial vessels occurs more com- 
monly in persons with a tendency to hypertension, but in many cases there is 
no increase in pressure. Good statistics are not yet available, but it seems prob- 
able that women are as subject to the disease as are men and perhaps more so. 
There can be no question about the fact that a high percentage of persons are 
pulled down slowly and finally killed by this disease if only because at necropsies 
the pathologist finds the lesions so commonly. 

Etiology 

Little is known about the etiology. As already noted, the presumption is that 
the little thrombi come because of sclerotic injuries to the small blood vessels of 
the brain. The nature of many family histories suggests that there is a hereditary 
tendency to the disease. Occasionally one will see families in which several of 
the members were wiped out early in life by either cerebral or coronary thrombosis. 

Pathology 

Figures i to 5 show the common macroscopic lesions of the disease. In a 
typical case the brain is speckled with little black spots showing where thrombosis 
took place. With the microscope smaller brownish areas of atrophy can be seen. 
A few larger areas of softening may also be found, one of them perhaps represent- 
ing the thrombosis that brought about the patient's death. 

It will be seen that the lesions are different from those of Pick's and Alzheimer's 
disease. It will be seen also why, with these many little areas of destruction in 
silent areas, it is usually impossible for a neurologist to show weakness of any 
muscle or any abnormal reflex or anywhere a patch of anesthetic skin. 

Life History or the Disease 

Doubtless the best way in which to show the life histor}^ of the disease and its 
long clinical course will be to describe a few cases. 

Case Records of Little Strokes 

Case I. — An engineer of 66 years, secretary to a big corporation, came complaining 
of intestinal discomforts for which for years he had been treated strenuously by gastro- 
enterologists. The story, as told to the assistant who first saw the man, was a vague one 
of indigestion, colonic discomfort and feelings of "auto-intoxication ". Physical examina- 

VoL. VI. 1 147 



LIFE HISTORY OF THE DISEASE 



68(5) 




Fig. I. Results of thrombosis in many small arteries of the brain (from Alvarez). 



tion showed little that was noteworthy; the one significant finding probably was that he 
talked out of one side of his mouth. The blood pressure was 140 mm. Hg. systolic. 
Extensive laboratory tests and roentgenological examinations of the digestive tract failed 
to show any sign of disease. Later, during the course of three long interviews, the fol- 
lowing history was elicited with much difficulty. 

The man had enjoyed perfect health until 5 years before, when on July 18, 1930 at 
10:30 in the morning there came a series of short, severe, stabbing pains in the upper 
part of the head. He was much upset over this and "never felt right again". Another 
curious attack came 5 months later when a feehng of great lassitude flashed over him. 
Two months later he woke with a "head on him" as if he had been drinking heavily the 
night before. Actually he had not been drinking. When a physician arrived, he found 
an elevated blood pressure. After that morning the patient never had a comfortable 
moment. His bowels, which had always moved perfectly before, became constipated, 
and he felt that this was affecting his mind and producing a miserable feeling in his head. 
Largely for this reason he kept going to gastroenterologists. At times he had burnings 
and quivering feelings in his legs and hands. 

During the next 4 years he saw many physicians in a vain search for health. Various 

Vol. VI. 1 147 



68(6) 



CEREBRAL ARTERIOSCLEROSIS 




Fig. 2. Results of thrombosis of medium and small arteries (from Alvarez). 

diagnoses were made of colitis, auto-intoxication, anxiety neurosis and hypochondriasis. 

The significant points in the history appeared to be (i) that a lifetime of good health 
was terminated on a certain hour of a certain day, (2) that following the third sudden 
shock life became a burden, and (3) that the disease kept growing worse in steplike stager. 
As the man said, every few months he had a little "earthquake", and with each one of 
these he became worse. 

Further questioning elicited the fact that after one of these earthquakes there was a 
tendency for the right leg to draw up, and after another one his mouth filled with ropy 
saliva, as it does sometimes with injuries to the brain stem. Another one of his little 
strokes brought some hoarseness, another brought dribbling of urine, another made his 
walk unsteady. Important was the testimony of the secretary who had been with him 
for years. She noted that with the first shock he changed greatly; his handwriting be- 
came bad, his attention poor, his memory deficient and the organization of his thoughts 
so poor that she had difficulty in taking a letter from him. 

A significant symptom was the man's fear of being left alone. After a lifetime of 



Vol. VI. 1 147 



LIFE HISTORY OF THE DISEASE 



68(7) 




Fig. 3. Results of thrombosis of small arteries (from Alvarez). 



traveling in dangerous places without ever a bit of fear he became so afraid of being 
alone that he insisted on his sister's coming to live with him. 

Soon after this the man's mental processes became so disorganized that he was unable 
to work. It was no wonder that he told a rambling story and that it was difficult to get 
from him the really important details. 

Case 2. — A stout woman, aged 53 years, in the menopause, complained of attacks of 
epigastric pain and soreness in the abdomen. This had been bothering her for 20 years, 
but it had gotten worse in the previous 2 years. There were occasional spells of nausea, 
belching, vomiting and diarrhea. Food felt as if it were staying like a lump in the stomach. 

The woman had been examined roentgenologically many times, and little wrong had 
ever been found. For a time the systolic blood pressure had been more than 200 mm. 
Hg. Important was the fact that in the previous eighteen months, without any change 
in her diet, she had lost 30 pounds (13.6 kg.). She felt miserable all the time with a great 
sense of fatigue. 

Examination showed only a tender abdominal wall and hypertension. She was 
nervous and jumpy, and the deep reflexes were exaggerated. All the usual laboratory 
and roentgenological studies were negative. 
Vol. VI. 1 147 



68(8) 



CEREBRAL ARTERIOSCLEROSIS 




Fig. 4. Results of thrombosis in small and medium vessels and hemorrhage from a small 
vessel (from Alvarez). 



Finally after several long interviews the stor>' was obtained that she began to have 
trouble 22 years before, when at the age of 31 she suddenly felt her hands and arms go 
dead. For a time this left some weakness so that she could not safely carry things. Later, 
some of this weakness cleared up, but the deadness and discomfort in the arms remained. 
A few years before she was seen by the writer, she began to have curious spells of faint- 
ness. She had to stop driving her car because on two occasions she lost consciousness. 
After one of these spells the blood pressure dropped from the usual 200 to 135 mm. 
Hg. Then she had a spell in which she almost lost consciousness, and after that she 
was weak and dizzy; her handwriting became bad, and for a time she could not talk 
clearly. 

After one of the spells she felt so queer that she went to a psychiatrist. Then a 
coronary artery thrombosed, and she had a little anginal distress. Later in a spell she 
fell to the floor and was in coma for a day. In another slight spell her face was pulled 
to the left, and the right arm and leg were weakened. Following this she was laid up 
for a month and had to use her left hand for eating and writing. 
Vol. VI. 1 147 



LIFE HISTORY OF THE DISEASE 



68(9) 




Fig. 5. Results of thrombosis in small vessels. 



It was hard to say how much of this woman's abdominal distress was due to 
arteriosclerosis and the little injuries to her brain, but certainly her illness as a 
whole was due to a long series of slight apoplexies. One wonders also if the first 
spell at the age of 31 was due to the same disease process. It is probable that it 
was. One has to assume this because so many other patients with this disease 
tell a story of early attacks. 

This case illustrates the remarkable tendency patients with this disease have 
of complaining to the physician about everything but the little apoplexies. This 
disease must be suspected and then the story must be dug out with great per- 
tinacity. 

Case J. — A college president during the latter half of his life was subject to nervous 
breakdowns. The first came at about the age of 33 years and another 6 years later. On 
each of these occasions the man had to take a year off to recuperate. He would get tired 
and thin and unable to work, and albumin would be found in his urine. At the age of 
45 he had another breakdown so severe that he had to resign from his position. He was 

Vol. VI. 1 147 



68 (lo) CEREBRAL ARTERIOSCLEROSIS 

thought then to have either Bright's disease or tuberculosis. The course of events 
showed that he had neither disease but more probably an episode in the course of the 
cerebral arteriosclerosis which eventually killed him. 

After resting a year the man went to work again at an easier job. Two years later 
he had a sudden severe shock which nearly killed him. It was called a "heart attack", 
but at no time did he have any symptoms or signs of heart disease. Apparently he 
suffered from thrombosis of a fairly large intracranial artery because his character 
changed; formerly a lovable, good-natured Irishman, he now became irascible; formerly 
very clean and neat in every way, he now had to be urged to bathe and change his linen; 
formerly well mannered at table, he now ate coarsely. His employers saw the change 
and wondered if he were tippling in secret. Later, a little thrombosis hit his bulb and 
left his swallowing mechanism so impaired that with each meal food entered the larynx 
and caused a coughing spell. This difficulty continued to the end of his life. 

Repeated medical examinations failed to show anything wrong, except some hyper- 
tension. 

Then on a long journey he apparently had another stroke because again his character 
changed for the worse. He became careless about many things; he became more irri- 
table, and because of dribbling of urine his clothes began to reek of ammonia. Highly 
significant of the great change in his mentality was the fact that he never seemed to notice 
the odor or to feel any embarrassment about it. 

Then one morning on getting out of bed he found one leg too weak to hold him up, 
and at last his physicians began to suspect what was wrong with him. Shortly after this 
his employers had to let him go. He Hved on for several years until the age of 57. 
Every few months there would come a dizzy spell or an attack of weakness, and with 
each one of these shocks he died a little. More and more his judgment failed. Curiously, 
however, if he met an old friend or a stranger, he could still for a few minutes pull him- 
self together and be his old brilliant and merry self. Soon, however, he would slump 
and become morose again. His poor wife was nearly frantic trying to take care of him. 
Finally one day there came the last stroke with a coma from which he never wakened; 
he died a purely brain death with the heart and kidneys working well until the end. 

Case 4. — A woman at 56 was a stout, tireless, able person who had never been ill. 
For long she had had a systolic blood pressure of 200 mm. Hg., but it had never bothered 
her. Then, after much overwork, she began to fail and occasionally to have a dizzy spell 
with headache. During the next 3 years these attacks pulled her down until she had to 
give up her work. Then at 59 she had a big stroke with hemiplegia and complete aphasia 
but only slight mental confusion. During the next few months her weight dropped from 
190 to 100 pounds (from 86.2 to 45.4 kg.). Destructive changes promptly appeared in 
the right hip joint on the side of the paralysis. Her blood pressure also dropped to nor- 
mal. The hemiplegia and aphasia soon cleared up, but she was left for the rest of her 
days with great mental distress which was so awful that she craved death as a mode of 
escape. 

During the following 6 years she continued to have attacks of dizziness, nausea and 
vomiting, sometimes associated with mental distress. Usually she was prostrated in 
bed for a few days afterward. These were the attacks which are usually thought to be 
due to acute indigestion or Meniere's disease. At 66 she died from a good sized cerebral 

Vol. VI. 1 147 



LIFE HISTORY OF THE DISEASE 68 (ii) 

thrombosis, and necropsy showed the brain speckled with scores of Httle black and brown 
infarcts. In addition there were a few larger areas of softening. There were enough to 
account for all the dozens of little attacks which she had had. No other lesion was found 
in her body to account for the long illness. 

In this case the woman kept until her last days most of her old personality, her old 
interests, her intelligence and understanding, her good grooming, her sweetness of dis- 
position and her thoughtfulness for others about her. She still remained sociable and 
Hked to work a little around the house. 

Case 5. — An unusually able man always had had perfect health and driving energy 
until the age of 45 years. He then suddenly found himself so weak and tired that every 
day he had to push himself to work. Careful studies failed to show any sign of disease. 
Months later because of abdominal discomfort a surgeon removed the appendix, but this 
did not help, and to a large extent the man had to retire from business. A year or so 
later he had little attacks, which were thought to be due to heart disease, but the sub- 
sequent course of his disease suggested that they were more probably the result of 
paresthesia in the thorax due to thrombosis of small vessels in the brain. These attacks 
wore him down until he had to quit work. Fifteen years later he was still keen and 
friendly and well groomed and with many of his old interests in work and family. He 
went to his office occasionally but could not do much. Then his feet began to shuffle, 
and he became afraid of being alone. Later his face began to lose its expression, and 
soon he had a typical Parkinson's syndrome. In the next few years he got worse and 
wound up as a paralytic in bed. His brain kept pretty clear until the end. Death set 
him free 21 years after the disease began. 

Case 6. — A typical story of distress suddenly referred out from the brain into the 
abdomen was told by an able woman physician who one day when she was in her fifties 
suddenly felt as if something had been pulled in two in her abdomen. There was some 
shock, and for the next 6 weeks the woman lay in a hospital bed, greatly distressed men- 
tally and unable to sit up because of a feeling that her spine was gone. Months later 
she had another similar episode which again put her to bed for weeks. At no time was 
there any sign of injury to any abdominal organ. There was no peritonitis, and repeated 
roentgenological studies of the digestive tract showed nothing wrong. At no time was 
there any serious trouble with digestion. The patient gradually recovered and was well 
except for feelings of fatigue and poor health. 

The next case illustrates the way in which thrombosis of a small intracranial 
artery with a storm going down the vagus nerves can produce an overly irritable 
digestive tract with spasticity perhaps of the gastrointestinal muscle and ex- 
aggerated reflexes in the gut. 

Case 7. — A woman of 56 years, who looked much older than that, complained of 
spasmodic pain in the epigastrium and nausea, which came the minute she put any food 
or even water into the stomach. There was also weakness and loss of weight. Even the 
efi'ort of trying to eat wore her out. Careful roentgenological studies of the digestive 
tract showed what was probably the scar of an old duodenal ulcer. 

Questioning the husband finally brought out the story that after a lifetime of per- 
fect health the woman's trouble had all come 4 months before on a Tuesday, about 7 :30 

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68 (i2) CEREBRAL ARTERIOSCLEROSIS 

in the morning, while she was getting breakfast. She fainted and sank to the floor. For 
6 hours after regaining consciousness she was mentally confused and kept asking over 
and over again what had happened. With the fainting spell a strange feeling of distress 
and tingling shot into the left side of the thorax and abdomen. As soon as she tried to 
eat, she found she could not take anything without getting the spasm in her abdomen. 
A month later she had another little shock after which she had an aversion to food. 

On asking the husband if these spells had brought any change in character he said, 
"Yes, before this happened, she was such a wonderful woman, while now she is childish 
and forgetful and without interests, and I have to watch over her all the time". Four 
years later she had improved somewhat but still was depressed and far from normal. 

All these cases show that unless the physician happens to think of little apo- 
plexies and asks about them he will never get the typical story, and he will never 
suspect what is the patient's real trouble. 

There are many more cases in which an older person complains of indigestion 
with much misery and feelings of weakness and fatigue and depression. Es- 
pecially when ail the laboratory and roentgenologic studies are negative, the 
physician may suspect that the cause of the breakdown w-as a small apoplexy, but 
he will be unable to get any story of one. The diagnosis will then have to remain 
indefinite until with the passage of time definite strokes appear. 

Symptoms 

One of the most important points to recognize at the start is that a person 
can have a cerebral thrombosis bad enough to leave him with a damaged brain 
and inability ever to work again without causing any shock or great mental 
commotion. Many a highly intelligent person has reported that during an attack 
he was fairly certain that he was having a stroke and yet felt no mental distress 
or confusion. This absence of mental distress can explain why in innumerable 
cases, when it is obvious that an older person has suffered serious arteriosclerotic 
injury to the brain, it will be impossible to get any history of a small apoplexy. 
The episode may have gone unnoticed or unrecognized early in the day, or more 
probably it came during the night when the blood pressure was at its lowest 
and the tendency to thrombosis at its greatest. 

In many cases a severe morning headache may indicate that something went 
wrong during the night. That a fairly large stroke need not wake the patient 
was shown by a college dean who woke one morning to find that most of his 
previously phenomenal memory was gone. Aside from this he was perfectly well. 
A few months later while at dinner he suddenly felt his cheek go numb, and he 
was left with a permanent patch of anesthetic -skin. With this there was no 
mental confusion or even distress. Other patients have been thrown to the 
ground and perhaps so weakened that they had to spend the night on the floor, 
but they felt no mental shock. Others have suffered complete aphasia and 
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SYMPTOMS 68 (13) 

hemiplegia without loss of consciousness and without much, if any, clouding of 
the mental processes. Because of this lack of any shock it is probable that often 
a little apoplexy may come during the day without the victim knowing it. 

Common Manifestations of the Disease 

In innumerable cases in older persons it is impossible to tell at the time of the 
first consultations what is the meaning of a certain episode or the cause of a 
nervous breakdown which has come suddenly with feelings of exhaustion and 
weakness. Only later as more episodes come, or as a definite stroke appears, or 
as the patient's mentality suffers, or as his character and temperament change, 
can one become fairly certain of what happened in the first spell. 

Sometimes a patient says that he slipped or stumbled or fell, but the fact 
that for weeks or months afterward he was dizzy or unable to work or confined 
to a hospital will make it seem more probable that the fall was due to a slight 
stroke. 

"Acute Indigestion.^^ — As already noted, when an acute episode is associated 
with a storm going down the vagus nerves to produce nausea and vomiting and 
perhaps a curious paresthesia in the abdomen, the first physician to arrive on the 
scene usually makes a diagnosis of acute indigestion. Often, if he would study 
the patient more carefully, he would be told of a little numbness of an arm or a 
leg, a tendency to fall to one side when walking, or of difficulty in using the right 
hand, or he would note some weakness of one side of the face or some difficulty 
in speaking or swallowing. Often these phenomena clear up within a few hours 
or days, and the patient then forgets to speak of them. 

Falling Down or Falling Out of a Chair. — A common story is that the patient 
fainted or fell out of his chair. Often he promptly picked himself up, and then 
the essential part of the story is that afterward there came some paresthesia, 
dizziness, a little mental confusion or a change in character. 

For instance a production manager came because he had trouble in walking. 
He had the typical shuffling gait of an old man. The story obtained from his 
business associates was that some time before he had fallen out of his chair, and 
from that moment on he was a changed man. No longer would he initiate any- 
thing, and so far as possible he blocked initiative in his subordinates. Then his 
legs became weak, and finally he had to be retired because of his inefficiency. 
That was years ago, and he still shuffles and still is unable to do any work. 

Vertigo. — One of the commonest symptoms that go with an episode is vertigo 
or more often a feeling of giddiness or uncertainty about standing or walking. 
Rarely will there be deafness or ear noises to go with this. Obviously not every 
attack of dizziness or uncertainty is due to a minor apoplexy, but one should 
suspect this origin of the trouble particularly when the person is past middle age, 

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68(i4) CEREBRAL ARTERIOSCLEROSIS 

and when, following the attack, there came some prostration or change in character 
or inability to work. For instance, a previously healthy man of 55 years one night 
had an attack of vertigo so bad that he could not walk without help. The next 
day he went to work, but for 10 days he was uncertain of his balance. He sus- 
pected a stroke because his memory had suffered a bit and his writing was affected; 
he often put down a word which was not the one that he intended to write. He 
also for the first time in his life had severe morning headaches. His blood pressure 
was normal. 

Nervous Breakdown. — One of the commonest results of a small stroke is a 
nervous breakdown. Whenever a person past middle life has a poorly explained 
nervous breakdown and especially one that came suddenly at a certain minute 
of a certain day or was there at waking on a certain morning, the physician always 
should think of the possibility that a small blood vessel in the brain has become 
thrombosed. He must think of this all the more when, with rest and good hygienic 
care, months or years pass without any sign of improvement or recovery. 

Over emotionalism. — Occasionally one of the most trying symptoms of an 
arteriosclerotic nervous breakdown will be a tendency to cry. Often such crying 
is involuntary and not due to any feeling of sadness. 

Loss of Grooming. — In many cases one of the surest signs to make one suspect 
that a man has had a small stroke is a loss of grooming or of a desire to keep the 
body clean and neat and well dressed. It is highly significant of disease in the 
brain when an executive or a professional man begins to go around with his clothes 
spotted and unpressed and with his shoes unshined. This may be the most 
important and perhaps the only neurological sign that can be found. 

The Significance of a Stidden Fall in Blood Pressure. — When with an episode 
suggestive of apoplexy the previously high blood pressure drops to normal, one 
must always suspect strongly that there was a small stroke. If the physician is 
seeing the patient for the first time after an episode, he may suspect that there 
used to be hypertension when he notes some cardiac enlargement or a ringing 
second aortic sound or a high diastolic pressure and decided hypertensive changes 
in the retinas. In some cases then, if the consultant will ask about it, the patient 
will remember that someone told him he had hypertension or that his physicians 
remarked that the pressure dropped at the time of the spell. Sometimes the 
pressure will remain normal for years afterward, and sometimes it will climb back 
up again. 

Sudden Unexplainable Loss of Weight. — Commonly after a small stroke there 
will be a sudden and decided loss of weight. This may range from 15 to 100 
pounds (6.8 to 45.4 kg.). One suspects that it is due to an injury to one of the 
centers for homeostasis in the hypothalamus. Occasionally the only sign of a 
small stroke will be this loss of weight. Usually the weight then remains at the 
new level for the rest of the person's life. 
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SYMPTOMS 68 (15) 

Distress, Pain or a Paresthesia Referred out from the Brain into the Thorax or 
Abdomen. — Many a small stroke produces as its first or main symptom a pares- 
thesia, pain, distress, "flash of heat" or rending feeling referred out into the 
thorax or abdomen. When it occurs in the thorax, the diagnosis generally is that 
of coronary disease. When it occurs in the abdomen, gastroenterologists usually 
spend months or years hunting for a lesion. Similar disturbances are seen in 
some cases of encephalitis or brain tumor. 

Abdominal Distress Due to Increased Spasticity or Irritability of the Muscles or 
Nerves of the Wall in the Digestive Tube. — Occasionally after a small stroke the 
stomach and small bowel will become so irritable, reflexly active or spastic that 
the moment food or even water is swallowed there comes a painful spasm. Usually 
after some months much of this spasticity or irritability fades, and the patient is 
able to eat again. 

Bulbar Paralysis. — With a small apoplexy some patients get a slight bulbar 
injury which causes food to enter the larynx and to produce much coughing at 
table. Other persons have ropy saliva such as is seen with some lesions of the 
brain. Other patients begin to speak thickly. 

A Burning or a Bad Taste in the Mouth. — Women past middle age sometimes 
complain of a bitter or metallic taste or a burning feeling in the mouth or tongue 
or palate. In such cases nothing wrong can be seen in the mouth, and the fact 
that in some cases the distress is felt in only half of the tongue or palate shows 
that it is due to an injury to some nerve or nerve center. The fact that these 
distresses never are helped by any treatment and that they never go away, suggests 
again that they are due to some irreparable injury to the nervous system. 

Slight Anesthesia or Numbness of the Skin or Weakness of Muscles or Ataxia. — - 
Many persons after a slight apoplexy complain of numbness or a slight temporary 
weakness of a hand or arm, and others lose their ability to write easily or legibly. 

Changes in the Core of the Personality. — As already noted, with the first little 
stroke a person may become greatly changed and perhaps utterly miserable and 
without interest or joy in life. Other persons, who seem to have been hit much 
harder by the stroke so that they are left with some aphasia or hemiplegia, will 
retain the core of their personality untouched and will go on, as Pasteur did, 
working hard and doing good work. Thus a physician of 84 kept to the end of 
his life his interests, his good humor, his zest in life, his good medical judgment 
and his good grooming, in spite of the fact that in the last 5 years his memory for 
recent events was so destroyed that he could not even count off a dozen bills to 
pay a tradesman. After counting 4 or 5 he would forget and have to start over 
again. He kept on practicing medicine only by having constantly at his elbow 
his old office nurse who served as his memory for what he had done or started to 
do a few minutes before. 

Psychopathic Changes. — Many persons after a small stroke become more or 

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68 (i6) CEREBRAL ARTERIOSCLEROSIS 

less psychopathic. . The physician must ask about such changes because usually 
they will not be mentioned to him by either the patient or the family. For in- 
stance an elderly woman was brought to a physician for treatment of a carcinoma 
of the stomach diagnosed in her home town. \\'hen this diagnosis could not be 
confirmed, and the consultant noticed signs of an arteriosclerotic injur}^ to the 
brain, he asked the son if of late his mother had changed psychically. "Yes," 
he said, "that's curious, since her fainting spell 6 months ago, she hasn't trusted 
me. Formerly she adored me, but now she is so suspicious and secretive that the 
other day she wouldn't trust me even to deposit a little money in the bank for her. 
She insisted on going herself." Such changes in character are common, and es- 
pecially when they come suddenly, they are vers' helpful in making the diagnosis. 

Moral Deterioration. — Some old men with only one recognizable mild apo- 
plexy will lose moral sense and will soon get into scrapes with prostitutes, girls or 
designing women. Many lose their business judgment and begin to dissipate the 
family fortune. Many a family has been ruined by the behavior of a man in this 
condition. 

Many Patients Become a Problem in the Home. — The patient, who has had 
one or more little strokes and a great change in character, is often a terrible 
problem in the home. He or she may make a prisoner of a spouse or a daughter 
and will cramp the lives of the grandchildren. 

A Tendency to Insanity May Be Brought Out. — Occasionally what appears 
to be a small stroke will throw a patient into a disturbed mental condition which 
will resemble that of other members of the family who have gone insane. 

Agitated Depression. — Not infrequently a small stroke or perhaps a fairly 
large one, which is unrecognized at the time, will throw the patient into an 
agitated depression or into a nervous state bordering on this. Unfortunately 
the nature of this condition is commonly misunderstood by physicians who have 
never been taught to recognize it. They are so concerned over the patient's com- 
plaints of constipation or discomfort in the abdomen that they fail to realize the 
importance of the fact that the woman is wringing her hands and weeping and 
saying that her mental suffering is more than she can bear, or they fail to learn 
that, unable to sleep, she walks the floor every night in agony, keeping the family 
all upset. 

Parkinson^ s Syndrome. — A number of patients after small strokes wind up 
with a Parkinson's syndrome. 

Sudden Coming of Insomnia. — When a person past middle age, who has 
always slept well, suddenly and for no obvious cause finds himself or herself 
unable to sleep, one must suspect that there must have been a small injury to 
some center in the hypothalamus which has to do with sleeping. The trouble is 
similar to that which sometimes comes with an attack of encephalitis. 

Facial Pain. — A number of the atypical, puzzling and intractable types of 
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DIAGNOSIS 68 (17) 

pain in the face in older persons apparently are due to the little strokes. As one 
would expect, in these cases the injection of the nerves and tissues with large 
amounts of a solution of procaine will only numb the face and will not relieve 
the pain. Evidently the cause for this is higher up in the brain. 

Sudden Blindness. — Occasionally, as when the thrombosis occurs in the artery 
of the optic nerve or in a large retinal vein, the patient will suddenly go blind in 
one eye. 

Arthritis Coming Suddenly in Older Persons. — Because in some persons with 
hemiplegia arthritis promptly appears in one or more joints of the weakened 
limb, one must think of a minor apoplexy, when in an older person some joint or 
a number of joints (as in the wrist) suddenly become badly inflamed and swollen 
and with trophic changes in the skin around them. 

A Flare-up of an Old Migraine. — A little apoplexy sometimes causes an old, 
fairly silent migraine to flare up and cause much distress. 

Episodes without Permanent Residue Due Apparently to Spasm in a Small 
Blood Vessel of the Brain. — A number of physicians in the past have described 
the type of attack which appears to be due to spasm in a small intracranial 
blood vessel. In such cases a man may have aphasia lasting perhaps a half 
hour; he will get perfectly well, and in a few days or weeks he will have 
several repetitions of the trouble. This certainly suggests that an artery has 
closed down and then opened again. Occasionally a man will have an episode 
so severe that it leaves him with aphasia and a decided hemiplegia, and yet 
he will be all straightened out within a few hours. Many such cases reported 
in the literature show that also with this type of disease the patients go on and 
die with cerebral arteriosclerosis just as if they had been having little episodes of 
thrombosis. 



Diagnosis 

Because there are no laboratory tests or roentgenological examinations that 
will indicate to a physician that he is dealing with little strokes, the diagnosis 
must be made from the history. Even a complete neurological study will seldom 
turn up any defects in reflexes, sensations or muscle strength. The unfortunate 
feature is that rarely does a patient think of telling of a nervous breakdown with 
the all-important changes in mentality and character. Even the family rarely 
think to tell of the terrible problem they have at home and in the business. For 
this reason the physician is ahnost certain to miss the correct diagnosis, if he is 
not on the watch always for this disease, and unless in many cases he gets a hunch 
that the person sitting there before him is not the person that he or she was a year 
or two before. 

In many cases this hunch can be gained by noting what a man's business is. 

Vol. VI. 1 147 



68 (i8) CEREBRAL ARTERIOSCLEROSIS 

Perhaps the record states that he is president of a good-sized corporation, and yet 
it is perfectly obvious that the seedy-looking and mentally slo\ved-up man on the 
other side of the desk could never hold such a position. Then the physician must 
ask and find that the man is not working and perhaps has not been for one or 
more years. Next, questions must be asked to find out if the man's ill health 
came suddenly. Often the wife, if questioned, will tell of a day when her 
husband suddenly aged ten years or more and became almost a stranger to her. 
Business associates also can often date the man's illness from a certain day or 
week, when perhaps he "collapsed" or fell out of his chair. 

In many cases a good consultant should make the diagnosis of premature 
senility the minute the patient walks in, slowly, with uncertain and short steps. 
It may be noted also that the mental reactions to questioning are slow, and the 
patient is unable quickly to understand or later to remember simple instructions 
in regard to the several examinations. Sometimes one will suspect that the man's 
face has lost expression, or there will be a little twitching of the facial muscles on 
one side, or a tendency to talk out of one side of the mouth, or perhaps there will 
be a little drooling, or there will be a little food left on the chin or on the clothes. 

Occasionally there will be a tendency to whistle a bit wlien talking or to ho- 
hum often or to have peculiar tics. Sometimes there will be a tremor of the 
hands or of the head, but this may be familiar in type. 

Too Much Efnphasis May Be Paid to Unimportant Fi}idings. — The physician 
can easily be deceived as to the diagnosis, if during the examination he pays too 
much attention to little abnormalities that happen to turn up. If he is wise and 
experienced and thoughtful, he will not be entirely satisfied with the diagnosis 
of an old coronary infarct, or a heart murmur, or an old duodenal ulcer, or gall- 
stones or diverticulosis of the colon. These red herrings drawn across the diag- 
nostic trail must be disregarded because they cannot explain the great mental 
changes. The physician must remember that there is no abdominal disease which 
in a moment can change a bright, wide-awake, happy and efiicient person into a 
dull, discouraged, slowed-up invalid who cannot work. This is the essential point. 

One reason for the making of incorrect diagnoses in these cases is that a neurol- 
ogist is practically never called. The family doctor, who sees these patients 
first, usually is so impressed by the fact that there are digestive distresses or pains 
in the thorax that, when he calls a consultant, he sends for either a gastroenterol- 
ogist or a cardiologist, but even when he calls in a neurologist, the diagnosis will 
be missed, if the neurologist does not understand that a big change in character, 
loss of memory or a soup stain on the coat is a neurological sign every bit as im- 
portant as a positive Babinski or a Romberg sign. 

Pathognomonic Symptoms. — Often the pathognomonic point is that the ill- 
ness dates from a peculiar attack which came at a certain minute of a certain 
day. In other cases the most suspicious feature about a particular episode is 

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PROGNOSIS 68 (19) 

that it was one of a series, one or more of which were typical little strokes. At 
times in certain cases with our present knowledge it is impossible to say that a 
puzzling syndrome of great fatigue, feelings of weakness and indigestion in an 
older person is due to cerebral arteriosclerosis, but when during the next year or 
two the patient has a typical stroke or a series of them, the attending physician 
will start wondering whether the first illness was also due to a stroke that came 
in the night. 

Apparently pathognomonic is a big fall in blood pressure or a sudden loss of 
weight, following an episode. Other important signs are failure of memory, 
coughing and choking at meal times, difficulty in writing or in pronouncing words, 
burnings or distress in the mouth, paresthesia throughout the body, the sudden 
coming of insomnia, overemotionalism, an agitated depression or the sudden loss 
of vision in an eye. 

In some cases the physician must think of a brain tumor, but usually with the 
passage of time and the lack of steady progression or signs of increased intra- 
cranial pressure or destruction of certain nerves this possibility can be ruled out. 
One has to think sometimes of the residue of an attack of encephalitis, and in 
occasional cases the differential diagnosis between this disease and small apo- 
plexies is impossible. 

Occasionally a roentgenogram of the base of the skull will show calcified in- 
ternal carotid arteries, and this will support the diagnosis of cerebral arterio- 
sclerosis. 

Prognosis 

The prognosis in these cases usually is poor and often hopeless. When damage 
has been done to an important part of the brain, and the patient has become 
apathetic and without any interest or joy in life, there is not likely to be much 
recovery. Aphasia with hemiplegia can disappear within a few days or weeks to 
leave the patient still energetic and efficient and happy, and then again an un- 
recognized apoplexy coming during the night can leave the victim a hopeless 
wreck. In the latter type of case there is little that can be done even in a pallia- 
tive way. 

It is important that the physician make the correct diagnosis so that he will 
not injure his reputation by promising a cure. It will help also to keep him from 
wasting his time on repeated overhaulings of the patient, long treatments and 
perhaps, from performing a futile operation or two. In these cases it is bad to 
remove remaining teeth because commonly the patient cannot afterward wear 
plates, his misery is greatly increased, and he goes down hill more rapidly than 
before. 

In many cases the patient's family should be informed as to the situation so 
that they can prepare for the future. Sometimes they must promptly sell a 
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68 (2o) CEREBRAL ARTERIOSCLEROSIS 

business, or they must guard the invahd so that he will not make bad investments 
and wreck the family fortune. They must be advised not to waste all their 
savings on many overhaulings and foolish treatments. Also, if they understand 
what has happened to the brain of their loved one, they may be kinder, more 
sympathetic and more forgiving. Business associates and employers should often 
know what is happening so that they can retire the man quickly before they suffer 
financial loss and perhaps the demoralization of a department. 

As already noted, there are cases like that of Pasteur in which a severe stroke 
with hemiplegia does not keep the victim from doing good work for the remainder 
of a fairly long life. 

The Interval between Episodes. — One encouraging fact is that some patients 
will have one or more definite small apoplexies and will then go for from lo to 
1 5 years without having another. A man can even have so bad a stroke that he 
lies comatose for 2 weeks, finds himself afterward with a hemiplegia and aphasia 
and yet can recover beautifully. 

The big trouble with many persons, who have had a small stroke, is that they 
go in daily dread of another one. They must be exhorted not to do this and must 
be told that they may go 10 years or even more before another stroke comes. 

Treatment 

The subject of treatment must be divided into that of the episodes and that 
of the disease. 

Treatment during an Episode. — With a severe episode the patient will have 
to stay in bed for a few days at least until the dizziness and mental confusion 
pass. Nowadays it is unfortunate that many of these patients are told that they 
have heart disease and are kept in bed for weeks or months and not allowed even 
to go to the bathroom. Obviously, if the patient hasn't coronary thrombosis, he 
or she should be gotten up as quickly as possible. Even when the physician 
makes the correct diagnosis, he may keep the patient in bed too long because 
of fear that being up and about will bring another spell. This fear is not justified 
by theory or experience. The mistake is made of thinking that the stroke was 
due to hemorrhage. Today it is known that hemorrhage is rare, and thrombosis 
is common. As NafTziger some time ago pointed out, since the little apoplexies 
are almost always due to thrombosis of a blood vessel, it is not logical to try to 
lower the blood pressure; actually it would be more logical to try to raise it. 

Often the family should be exhorted to "let up" on the aged relative and to 
stop hounding him or her to "snap out of it". These persons cannot much help 
themselves when the brain is badly injured. 

Care of the Patient between Episodes. — Since most patients and their families 
put their trust in medicine, it is often well to give something, and a good drug is 
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BIBLIOGRAPHY 68 (21) 

iodine because it has long been thought to keep arteries soft. Lipoiodine is a 
pleasant preparation to take, and one can give one or two tablets each day, 
intermitting every two weeks for a few days to avoid getting cumulative eflfects. 

Soporifics may have to be given if the patient has much difficulty in sleeping. 
Sedatives also may give a little relief from terrible mental anxiety and suffering. 
Unfortunately no drug has yet been found to restore to these patients their old 
energy, their sense of well-being and their joy in living. 

In some cases physical therapy will be helpful, especially when muscles are 
weak or when tissues and joints are aching. In some cases sweat baths will be 
soothing and helpful. 

Many physicians will ask, "should the patient be told what is wrong with 
him?" In many cases, ''Yes". So often the patient has a good idea as to what 
happened to him, and he will have more faith in a physician who at least discusses 
the possibility that there was a little stroke. The patient is happier also if he 
can frankly discuss the condition with someone. It will take away some of his 
feeling of loneliness and fear. 

As always, one must tell the patient only that amount of truth which he 
cares to face, or which he can understand or react to properly. Some persons 
prefer not to be told what is the matter with them, and then obviously the truth 
should not be forced on them. A few resent it and are outraged the more when 
other physicians, seen later, feel that the idea is preposterous. Highly alarmist 
and neurotic or stupid persons, therefore, had better not be told. In other cases, 
in which the physician feels that he had better say something about an injury 
to the brain, it will be less alarming to speak of a temporary spasm in a little 
blood vessel rather than of an irrevocable plugging by a thrombus. Few persons 
seem to object to the idea of spasm, and often it reUeves their minds because it is 
less alarming than the thought of hemorrhage which had come to them. This 
diagnosis has the great advantage also that it may be accepted by the physicians, 
who later see the patient; it is not so abhorrent to them as the idea of thrombosis. 

When the blood pressure is high, or when there is severe morning headache, 
it may help to give potassium thiocyanate in doses of from 3 to 9 grains (0.2 to 
0.6 gm.) a day. The drug can be poisonous and, therefore, its administration 
should be watched and guided by determinations of the amount in the blood 
from time to time. 

If vertigo is troublesome, the physician can try lowering the amount of sodium 
chloride in the diet, or he can desensitize to histamine or try giving nicotinic acid 
or prostigmine. 

BIBLIOGRAPHY 

I. CRITCHLEY, M.: The neurology of old age (Goulstonian lecture). Lancet, 1931, 1, 
1119, 1221 and 1331. 
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68 (22) CEREBRAL ARTERIOSCLEROSIS 

2. CRITCHLEY, M.: Discussion on the mental and physical symptoms of the presenile 

dementias, Proceed. Roy. Soc. Med., 1933, XXVI, 1077. 

3. JANEWAY, T. C: A clinical study of hypertensive cardiovascular disease. Arch. 

Int. Med., 1913, XII, 755. 

4. OSLER, W. : Transient attacks ol aphasia and paralysis in states of high blood pres- 

sure and arteriosclerosis, Canad. Med. Assoc. Jour., 1911, I, 919. 

5. ALVAREZ, W. C. : Small commonly unrecognized apoplexies, Geriatrics, 1946, 1, 189. 

September i, 1947. 



Vol. VI. 1 147 



CHAPTER III 

ENCEPHALITIS AND OTHER \TRUS INFECTIONS 
OF THE CENTRAL NER\^OUS SYSTEM 

Bv GORONWY O. BROUN 

Table ok Coxtfnts 

Historical Account ^2 

Classification of Encephalitis jr 

Group I Types of Encephalitis Occurring C'licflv in the \\'inter 

and Earlv Spring yg 

Lethargic Encephalitis yg 

Synonvms ng 

Definition jg 

Historical Account and Incidence 78 

Seasonal Incidence yo 

Age and Sex hicidence 81 

Alortalitv 82 

Etiology 82 

Pathology 82(4) 

Clinical Course 82(5) 

Laboratorv Findings 82(7) 

Post-encephalitic Parkinsonism 82(9) 



Ps\chic Alterations 

.Mental Instabilit\- 82 

Differential Diagnosis 82 

Treatment 82 

Specific Treatment 82 

Chemotherapy 82 

General Measures 82 

Treatment of Neryous Sequelae 82 

Surgical Treatment of the Residuals of Encephalitis 82 

Herpes Simplex Encephalitis .82 

Post-infectious Encephalitis 82 

Post-influenzal Encephalitis 82 

Encephalitis Following .Measles 82 

German .Measles Encephalitis 82 

COPYRIGHT 1950 BY THE OXFORD UNIVERSITY PRESS, IXC. 

69 



II) 
II) 
13) 
16) 
16) 

17) 
18.) 

18) 
21) 
21) 
22) 

26) 

27) 



70 ENCEPHALITIS AND OTHER MRUS INFECTIONS 

OF THE CENTRAL NER\ OUS SYSTEM 

Encephalitis Following X'^ariola (Small Pox) 
Post-vaccinal Encephalitis . 

Patholog\' 

Onset and Clinical Course . 

Encephalitis Following Chicken Pox- 
Encephalitis Following Mumps 

Encephalitis Accompanying Infectious .Mononucleosis 
Encephalitis Following Whooping Cough 
Group II: Types of Encephalitis Occurring Chieflx in Late 
Spring and Early Summer 
Russian Spring-Summer Tick Borne Encephalitis (Forest 

Spring Encephalitis) 

Definition 

Historical Account 

Geographical Distribution 

Incidence 

Epidemiology 

Etiology . 

Characteristics of the \^irus 

Pathology 

Clinical Course 

Differential Diagnosis 

Preventive Measures 

Treatment 
Group III: Types of Encephalitis with Time of Onset Chiefl\- 
but not Exclusively in the Late Summer and Autumn 
Epidemic Summer Encephalitis, St. Louis Type 

Definition 

Historical Account 

Geographical Distribution 

Climatic Conditions 

Age and Sex Incidence 

Mortality 

Etiology and Epidemiology 

Pathology 

Incubation Period 

Clinical Course 

Laboratory Findings 

The Virus Neutralization Test 

Residuals of St. Louis Encephalitis 

Differential Diagnosis 

Treatment 

Equine Enccphaloni\'elitis 

Introduction 

Eastern Equine Encephalomyelitis 

Definition 

Voi., \T 750 



82 


[27) 


82( 


28) 


82 


.29) 


82 


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82 


^0) 


82 


..^0 


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43) 


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43) 


82( 


44) 


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46) 


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46) 


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47) 


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TABLE OF CONTENTS 



71 



Incidence, Etiology and Epidemiology 

Pathology 

Clinical Course 

Differential Diagnosis 

Treatment and Prevention 

\\'estcrn Equine Encephalomyelitis 

Definition 

Historical Account 

Etiology and Epidemiology 

Age and Sex Incidence 

Pathology 

Clinical Course 

Differential Diagnosis 

Prevention and Treatment 

Venezuelan Equine Encephalomyelitis 

Japanese Type B Encephalitis 

Definition 

Historical Account 

Geographical Distribution 

Climatic Conditions 

Age and Sex Incidence 

Case Incidence and Mortality 

Etiology and Epidemiology 

Pathology 

Clinical Course 

Laboratory Findings 

Nervous Residuals 

Treatment 

Australian X-Disease 

\^'est Nile Encephalitis 

Group W: Encephalitis and \'^irus Meningitis with Irregular 

Seasonal Distribution 

Lymphocytic Choriomeningitis 

Synonyms 

Definition 

Introduction and Historical Account 

Geographical Distribution 

Etiology and Epidemiology 

Pathology 

Clinical Course 

Laboratory Findings 

Differential Diagnosis 

Treatment . . 

Louping 111 . . 

Bibliography 

Vol. y\. 750 



82 


(63) 


82 


(64) 


82 


(64) 


82 


(65) 


82 


(6,-) 


82 


(66) 


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82 


(66) 


82 


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82 ( 


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82( 


78) 


82( 


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82( 


78) 


82( 


78) 


82( 


79) 


82( 


80) 


82( 


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72 ENCEPHALITIS AND OTHER MRUS INFECTIONS 

OF THE CENTRAL NER\'OUS SYSTEM 

Historical Account 

The early history of encephaHris hke that of other specific infections 
remains shrouded in uncertainty. Somnolence and coma occurring 
during the course of febrile illness are phenomena so common and so 
strikinor that the\' could not well be overlooked even by the most 
unskilled observer. The practice of careful clinical study, so strongly 
developed in the school of Cos, naturally led to the recognition of cases 
of this type. Hence, it is not surprising that the writings of Hippocrates^ 
record numerous instances of fever accompanied by delirium and coma. 
In "the Epidemics" several case reports appear in which findings still 
more suggestive of encephalitis are described. Thus headache and neck 
rigidity coupled wkh fever, delirium and coma are recorded in one 
instance and in another instance tremors of the hands and facial palsy 
accompanied by fever and delirium. Following this period similar indi- 
vidual cases are reported often. Occasionally even widespread epidemics 
are described which fit fairly well into the clinical picture of what we 
now call encephalitis. Hecker', writing before the bacteriological era, 
describes several epidemics of "encephalitis" occurring in Germany in 
1480 and 148 1 and again in 1504, 1505 and 15 17. In 1482 he notes an 
outbreak of "febrile cerebritis" in France and in 1529 a "languor resem- 
bling syncope" in Pomerania. Sydenham^ described an epidemic of 
"febris comatosa" observed in England in 1673-75. Stern^ quotes a case 
described by Albrecht von Hildeshein in 1695, which appears to resem- 
ble closely the picture of lethargic encephalitis. The occurrence of an 
outbreak of "sleeping sickness" in Tubingen in 1712 was noted by von 
i'.conomo'^ in his first discussion of lethargic encephalitis. 

In all of these early descriptions of conditions suggesting encephalitis 
it is difficult to exclude in some instances the delirium and coma common 
to all overwhelming febrile illnesses and in others bacterial infections 
such as meningitis and brain abscess. Until the development of the 
sciences of bacteriology and pathology and the introduction of the 
clinical study of the cerebrospinal fluid, no reliable basis for these dis- 
tinctions were available. Therefore, it is to be expected that our knowl- 
edgre concerning^ the differentiation of virus infections of the nervous 
system from bacterial infections is largely of recent date. The recogni- 
tion of the multiplicity of types of encephalitis and the isolation and the 
study of the viruses giving rise to them are even more recent and no 
doubt still far from complete. 



HISTORICAL ACCOUNT 73 

Among the virus infections of the nervous system there is one, rabies, 
which is so striking in its manifestations and so dramatic in its mode of 
spread that it was recognized readily even in ancient times. Rabies was 
known to Hippocrates and Aristotle as well as in all subsequent periods. 
The usual connection between the bite of a rabid animal and the onset 
of this disease, together with its painful spasmodic symptoms, readily 
distinguishes it ordinarily from all forms of encephalitis. 

Poliomyelitis was the next virus infection of the nervous system to 
win definite clinical recognition. This disease was, perhaps, described 
by Underwood in England as early as 1774. Its separation as a distinct 
clinical entity dates from the work of Jacob von Heine" in Kolmar, 
Germanv^ in 1840. Strumpell' as long ago as 1885 showed that this 
disease occurs in an encephalitic form. Sometimes it occurs concurrently 
with epidemics of the summer types of encephalitis, thus complicating 
the differential diagnosis. 

In 1890 Leichtcnstcrn~* observed cases of "influenzal" encephalitis 
during the pandemic of this disease which occurred at that time. About 
the same time a disease, which was given the name of "nona"', was 
described also. It has been suggested that this may have been a form of 
influenzal encephalitis, but in the disease entities recognized at the 
present time its place remains uncertain. 

Since the viruses, which cause influenza, are now known, the rela- 
tionship of these viruses to encephalitic infections occurring in associa- 
tion with this disease has been the subject of some study. It has not yet 
been established that the influenza viruses actually cause encephalitis 
in man^^\ 

If we study the medical texts^" of the period of the early years of the 
present century, we find that recognition was given to the encephalitic 
form of poliomyelitis, to post-influenzal encephalitis as well as to that 
following other infectious diseases such as mumps and to toxic encepha- 
litis, for example that occurring in lead poisoning. This represents the 
extent to which our knowledge of encephalitis had developed in the first 
decade of the present century. 

During the course of the first World War numerous cases of an 
unusual type of infection involving the central nervous system were 
noted in Europe, probably first in Rumania" and somewhat later in 
France'-. Finally in 191 7 a group of these cases were studied and de- 
scribed as a definite clinical entity by von Economo^ of Vienna under 
the name of lethargic encephalitis. The onset of this illness occurred 
chiefly in the cooler months of the year. 

Vol. VI. 750 



74 ENCEPHALITIS AND OTHER VIRUS INFECTIONS 

OF THE CENTRAL NER\'OUS SYSTEM 

Almost simultaneously with the recognition of lethargic encephalitis 
in Europe another disease was described in Australia, having many 
features in common with it. This mysterious infection was called 
Australian "X" disease'^ '\ It occurs chiefly during the warmer months 
of the year in Australia and hence must be considered one of the "sum- 
mer" types of encephalitis. 

In 1924 a definite and severe summer epidemic of encephalitis took 
place in Japan. This was studied bv many investigators including 
Kaneko and Aoki^' and by them was distinguished from winter (lethar- 
gic) encephalitis bv various clinical as well as seasonal features. They 
suggested that the winter form of encephalitis be called type A, the 
summer form, type B. Other epidemics of summer encephalitis occurred 
in Japan in 1929, 1935 and 1937, and considerable numbers of sporadic 
cases were observed in the intervening years'*'. Our knowledge of this 
infection recently has been increased through the studies of Sabin'" and 
others associated with the American forces occupying Okinawa and the 
Japanese Islands. 

An epidemic infection verv^ similar to Japanese encephalitis appeared 
in the United States during the summer of 1932 in Paris, Illinois. The 
following year it reappeared in and around St. Louis, Missouri'^ as well 
as in other parts of the mid-western states. This disease has been termed 
St. Louis encephalitis. It definitely has its highest incidence in August, 
September and October. 

In 1933 and 1934 Rivers and Schwentker'* described the accidental 
laboratory infection of human beings with "louping ill", a virus disease 
of sheep which involves the central nervous system. A form of encepha- 
litis occurring chiefly in the springy and early summer has been recognized 
for a number of years in the U.S.S.R.-^^ Casals-"' has found this disease 
to be serologically closely related to "louping ill". 

As early as 1925 W'allgren''' gave a clinical description of cases of 
an unusual type of meningitis which he termed lymphocytic meningitis. 
In 1934 Armstrong and Lillie'" reported the isolation of a virus which 
subsc(]ucntly they have shown to be the causative agent of this disease. 

\ etcrinarians have recognized an encephalomyelitis of horses for 
many years. In 193 1 the virus responsible for this disease in the western 
portion of the United States was described by Meyer, I laring and 
Howitt"'. Several years later a different virus causing a similar infection 
in the eastern portion of the country was recognized by 1 en Broeck""". 

Vol. \'I. 750 



CLASSIFICATION 



75 



Human infection from both of these varieties of equine encephalomye- 
litis, as well as a third variety now recognized in South America"", is 
known to occur. 

In 1940 a neurotropic virus was isolated in Uganda, Africa"*", which 
is known as West Nile encephalitis virus. 

The occasional isolation of viruses resembling that of herpes simplex 
from cases of lethargic encephalitis aroused interest in the possibility that 
this virus might be a cause of human encephalitis. This fact was estab- 
lished through the isolation of the virus and the demonstration of intra- 
nuclear inclusion bodies in a fatal case of encephalitis by Smith, Lenette 
and Reams^*^". 

The isolation of the virus causing mumps led to renewed interest in 
the neurological symptoms which follow this infection"'' '"^ 

While encephaUtis following smallpox is rare"\ vaccination against 
this condition in certain European countries has been followed by 
encephahtis with sufficient frequency to cause considerable attention 
to be devoted to it^'^\ Chicken pox also occasionally is complicated by 
encephalitis""^ 

Measles, a known vims infection, not infrequently is followed by 
the occurrence of encephalitis'*^ The relation of the measles virus to 
this infection is not estabhshed, but this must be recognized as a definite 
post-infectious type of encephalities. German measles likewise may 
have encephalitis as a sequel'^^ 

Pertussis considered to be of bacterial origin is complicated at times 
by evidences of damage to the central nervous system"". Simple hemor- 
rhas^es may be a possible cause, but the occurrence of encephalitis can 
not be excluded. 

Infectious mononucleosis, the cause of which still is obscure, is fol- 
lowed by neurological symptoms with sufficient frequency to justify 
inclusion in this discussion^''^ 



Classification of Encephalitis 

The preceding review of the history of the recognition of the various 
forms of encephalitis indicates that a classification of the virus infections 
of the brain and meninges must take into consideration the specific types 
listed in the following outline. 

Vol. VI. 750 



76 ENCEPHALITIS AND OTHER VIRUS INFECTIONS 

OF THE CENTRAL NERVOUS SYSTEM 

GROUP I 

T\'pes of encephalitis witii time of onset chiefly, hut not exclusively, 
in the winter and early spring. 

( 1 ) Encephalitis lethargica of von Economo, also called epidemic 
encephalitis and encephalitis type A of Kaneko and Aoki 

(2) I lerpes simplex encephalitis 

(3) Post-infectious encephalitis, which includes: 

(a) Post-influcnzal encephalitis 

(b) Encephalitis following measles and German measles 

(c) Encephalitis following small pox 

(d) Post-vaccinal encephalitis 

(e) Encephalitis following chicken pox 

(f) Encephalitis following mumps 

(g) Encephalitis accompanying infectious mononucleosis 
(h) Encephalitis following w^hooping cough 

GROUP II 

Types of encephalitis with time of onset chiefly in the late spring 
and early summer. 

(i) Russian spring-summer tick-borne encephalitis, also called 
forest spring encephalitis. Possibly identical with louping ill. 

GROUP III , 

Types of encephalitis with time of onset chiefly but not exclusively 
in the late summer and early autumn. 

( 1 ) St. Louis encephalitis 

(2) Eastern equine encephalomyelitis 

(3) AVestern equine encephalomyelitis 

(4) Venezuelan equine encephalomyelitis 

(5) Japanese type B encephalitis 

(6) Australian "X" disease 

(7) West Nile encephalitis 

(8) Encephalitic forms of poliomyelitis 

GROUP IV 

Encephalitis and virus meningitis with irregular seasonal distribution, 
(i) Lymphocytic choriomeningitis 

(2) Louping ill 

( 3 ) Rabies 
Vol. VI. 750 



CLASSIFICATION 77 

In addition to these, certain bacterial, protozoal and toxic forms of 
encephalitis occur but will not be included in this discussion. 

The discovery of so many types of virus infections of the nervous 
system within a relatively short period of time has caused some confusion 
in regard to the classification of these diseases and has created problems 
in nomenclature, epidemiology, differential diagnosis, prevention and 
treatment, many of which remain unsolved. 



Vol. y\. 750 



78 ENCEPHALITIS AND OTHER VIRUS INFECTIONS 

OF THE CENTRAL NER\ OUS SYSTEM 

GROUP I 

Types of Encephalitis Occurring Chiefly in the Winter 
AND Early Spring 



LETHARGIC ENCEPHALITIS 

Syiionyyns. — Encephalitis lerhargica (von Economo); enceph;ilitis 
type A (Kaneko and Aoki); winter encephalitis; epidemic encephalitis. 

Depnition. — Lethargic encephalitis is an infectious disease, probably^ 
caused by a neurotropic virus, occurring at all seasons but most com- 
monly in the colder months of the year, characterized by focal lesions 
of the brain, involving particularly the basal ganglia, pons and medulla, 
characterized by somnolence, cranial nerve palsies and an irregular fever 
It exhibits a high initial mortality and in non-fatal cases often is followed 
by serious chronic nervous sequelae. 



Historical Account and Incidence 

It is generally accepted that the first cases of lethargic encephalitis 
to be recognized occurred in Rumania during the months of April and 
May of 1915'^ and were reported in 19 16 under the title of "encephalite 
hemorrhagique avec un diplocoque encapsule" by Obregia, Urechia and 
Carniol". In the following year 40 cases were reported from the French 
military^ hospitals by Cruchet, Alontier and Calmettes^". These cases had 
their dates of onset during 191 5 and 19 16. Further cases were reported 
by Etienne"\ some of which were seen during ^August of 19 15. The 
cases of Etienne, if accepted as being true cases of lethartric encephalitis, 
indicate that the onset of some cases occurred during the summer time 
even at this early stage of the pandemic. 

Von Economo's report^ which was given before the Vienna Society 
for Psychiatry and Neurology on April 17, 19 17, usually is credited 
with being the first in which there was recognition of this disease as a 
definite clinical entity. He also suggested the term "lethargic encepha- 
litis", which has continued to be applied to this disease by many writers. 
Yon I'.conomo's cases occurred in V^ienna and had their onset in the early 
months of 19 17. 

Vol. VI. 750 



LETHARGIC ENCEPHALITIS 79 

The work of von Economo was confirmed and extended by the 
Medical Research Committee of the British Ministry of Health-^ Alari- 
nesco and Mcintosh, working for this committee, estabUshed definitely 
the fact that cases of encephahtis, which were observed in Enjrkind, were 
identical with those described by von Economo in Austria and by 
Netter-*' in France, and that encephalitis is a disease sui generis, anatomi- 
cally and clinically distinct from analogous affections. 

From 19 1 7 onward cases of the disease were recognized in various 
parts of Europe-'. By the summer and autumn of 19 18 the disease had 
been recognized in South America by Morquio-* and in the United States 
by Neal-^ Subsequently the disease has been found in practically every 
country in the world. An analysis of the figures on world incidence 
for the years 1919 to 1937 is given in Table I and shown graphically in 
Chart I. The pandemic reached its peak in Europe in I92o-^ but in 
Canada and the United States the year 1923 marked the o-reatest inci- 
dence. The available figures for the world incidence of the disease show 
very well defined peaks occurring in 1920 and 1924 with less evident 
peaks in 1929 and 1933. From the time of the second peak in 1924 to 
the present date there has been an almost continuous decline in the 
number of cases reported, provided the summer cases of Japanese 
encephalitis and St. Louis encephalitis are omitted. 

The first column in Table I shows the total number of cases of 
encephalitis reported throughout the world from 1919 throuo-h 1937. 
Cases of Japanese encephalitis and St. Louis encephalitis are listed in sepa- 
rate columns. The final column, which shows the number of cases of 
encephalitis in each year after the known cases of summer encephalitis 
are subtracted, is the best approximation that can be made of the world 
incidence of lethargic encephalitis. 

Seasonal Incidence 

The ease with which lethargic encephalitis can be confused with a 
number of other virus infections of the brain renders the reports of its 
seasonal incidence subject to the errors of inaccurate diagnoses. Never- 
theless, in the early years of the world-wide pandemic, w hich began in 
191 7, the higher incidence of encephalitis during the cooler months of 
the year was quite definite. 

The summary of official reports on seasonal occurrence of enccpha- 

VoL. VI. 750 



8o ENCEPHALITIS AND OTHER VIRUS INFECTIONS 

OF THE CENTRAL NERVOUS SYSTEM 

litis oriven by the Ahitheson Commission for the years 1919-27 shows 
clearly the general seasonal trends'l In the year 1920, which marked 
the first peak of this epidemic, there was a marked increase of cases 
beoinniniT in December of the preceding year and ending in Alay with 
the £Treatcst incidence in February and March. Subsequent years show 
this seasonal difference much less strikingly. In 1924 a severe outbreak 

TABLE I 

A^'oRi.D Incidence Ok Encephalitis* 

Total Cases Total Cases Mirms 

From Available Total Japanese Total Missouri Kiioivii Sirntmer 

Year Official Reports Type "B" Cases ''Siw/vier" Cases Epidemic Cases 

1919 962 962 

1920 9^824 9^824 

192 1 5.' 39 5'i39 

1922 2,601 2,601 

1923 5-^44 5'244 

1924 16,002 6,125 91877 

1925 7,606 139 7467 

1926 7ii4i 864 6,277 

1927 4>387 1,006 3«38i 

1928 5i73- 70 5)662 

1929 7,763 2,058 5,705 

1930 5,017 499 4,518 

193 1 4,385 129 4,256 

1932 4,792 689 4,113 

1933 7^674 791 1.648 5,235 

1934 4,037 278 41 3,718 
J935 8,542 5,370 19 3,153 

1936 3,673 1,305 5 2,363 

1937 4,265 2,030 518 1,717 

• These figures have been taken from the First, Second and Third Reports of the 
.Matheson Commission, from the U. S. PubUc Health Service Weekly Reports, from the 
U. S. Bureau of the Census Reports; and also from the Reports of the Health Depart- 
ments of St. Louis City and St. Louis County and Reports of the Missouri State 
Department of Health. 

of encephalitis took place in England, Wales, Scotland and Ireland. This 
outbreak showed its greatest prevalence in June of that year, and even 
the summer months of July and August showed a high incidence. From 
this time onward the seasonal variation in cases of encephalitis in British 
Isles has been very slight. 
Vol. VI. 750 



LETHARGIC ENCEPHALITIS 8i 

On the continent of Europe this 1924 summer outbreak does not 
appear in the statistical reports, and the predominance of winter cases, 
\\hiie not so striking as ni the early years of the pandemic, still continues 
through the year 1929. However, again referring to world incidence 
as shown in Table II on page 192 of the Matheson"' report, if all cases 
occurring in the winter and spring months, that is from December of 
one year through May of the following year, are totaled and compared 
with the total number of cases occurring in the summer and the autumn, 
that is between June ist and the end of November, the first group pre- 
dominates in each annual period. The only exception to this rule would 
occur, if the cases of the summer epidemic of encephalitis, which oc- 
curred in Japan in 1924, are included. 

This reversal of seasonal distribution in the presence of an epidemic 
summer encephalitis is worthy of note and perhaps may be used in the 
detection of local increase even of sporadic cases of summer encephalitis 
in any locality. At the time \^^hen summer epidemics occur the seasonal 
change in incidence stands out sharply. The cases occurring between 
June and November definitely exceed those occurring between Decem- 
ber and the end of May. 

The apparent decreasing seasonal specificity"^ of lethargic encepha- 
litis may be due to an actual change in the seasonal character of the 
disease. On the other hand, in view of our increasing knowledge of the 
summer types of encephalitis, it may be suggested that the general inci- 
dence of the winter cases has fallen to the point where sporadic cases of 
summer encephalitis now serve to level off the seasonal incidence. This 
is even more likely to be the case in the L^nited States and Japan, where 
the summer types of encephalitis are known to be endemic. 



Age and Sex Incidence 

Lethargic encephalitis occurs at all age periods but is most common 
in young adults. Of 7,584 cases collected by the Matheson Commission-', 
in which the age was stated, the group between 20 and 30 years of age 
showed the highest incidence of occurrence. Those between 10 and 20 
years of age stand next. In all other age groups there were fewer cases. 

Statistics indicate that approximately 60 per cent, of the cases occur 
in males and 40 per cent, in females". No special racial susceptibilities 
have been shown to occur^. 

Vol. VI. 750 



82 ENCEPHALITIS AND OTHER \ IRUS INFECTIONS 

OF THE CENTRAL NERVOUS SYSTEM 

Mortality 

Alortality figures are extremely variable. In a series of 3,558 cases, 
traced and investigated in England and Wales, it was 33.5 per cent., 
varying considerably from year to year"^ During the extensive epidemic 
of 1924 the mortality rate was 27.9 per cent., while during the other years 
it has averaged 51.7 per cent. In Switzerland during 1920 the case mor- 
tality rate was 29.5 per cent. During the years 192 1 to 1925 it was 64.2 
per cent. In 7,876 cases, collected from the literature by the Matheson 
Commission"^, the mortality was 50.5 per cent. 

During years of active epidemics there is more complete reporting 
of non-fatal cases, and during such years the official figures ordinarily 
show a lower mortality percentage than in years of lesser incidence, 
when fatal cases are reported, but non-fatal cases often do not get into 
the official records. It is noteworthy that in many countries, where 
encephalitis in recent years has been made a "reportable disease", the 
"deaths" reported as due to encephalitis often considerably exceed the 
number of "cases" reported. 

Little difference in mortality between the sexes is noted. Occasion- 
ally a slightly higher mortality in males is observed. Mortality is highest 
between fifty and sixty years of age but falls off in the higher age groups. 
It is also high in the first years of life. 

Etiology 

The etiology of lethargic encephalitis still remains uncertain. A 
voluminous literature has accumulated on the subject, \\ hich has been 
reviewed carefully in the three reports of the Matheson Commis- 
sion'*'- -'■ '\ 

It is now conceded that this disease is entirely distinct from polio- 
myelitis. The diseases differ in seasonal incidence, type of onset, usual 
symptomatology and distribution of pathological lesions. Investigators 
have failed to recover the virus of poliomyelitis by inoculation of mon- 
keys with encephalitis brain material, and the convalescent serum of cases 
of lethargic encephalitis fails to show neutralizing antibodies'^' against 
the virus of poliomyelitis. However, the clinical differentiation in a 
given case between the cerebral, bulbar and pontine forms of poliomye- 
litis and lethargic encephalitis may still occasionally constitute a problem 
in differential diagnosis. 

Vol. VI. 750 



LETHARGIC ENCEPHALITIS 82(1) 

The possible relationship between influenza and encephahtis has long 
been the subject of argument. Leichtenstern' described a type of en- 
cephalitis occurring in cases of influenza as long ago as the influenza 
epidemic of 1889-92. It would, therefore, appear that some form of 
encephalitis may occur not infrequently in association with epidemics 
of influenza. Whether this encephalitis is identical with the lethargic 
encephalitis, which occurred in pandemic form from 19 17 to the present 
time, is, however, a matter concerning which much controversy exists. 
The more or less simultaneous occurrence of the pandemics of the two 
diseases in the period between 1917 and 192 i, the influenza-like symp- 
toms that not infrequently mark the onset of encephalitis and finallv^ the 
appearance of evidences of parkinsonism and other nervous residuals, 
known to follow encephalitis, in individuals, whose history showed a 
previous illness diagnosed only as "influenza", naturally raised this ques- 
tion. However, it would appear that cases of encephalitis were noted in 
Rumania and France prior to the onset of the influenza pandemic"'^"". 
The possible identity of influenza and lethargic encephalitis was taken 
into consideration by von Economo^. In his first classical description of 
the disease he notes that there was no unusual prevalence of influenza 
in Vienna at the time he observed his first cases of encephalitis. 

The pandemic of encephalitis obviously was of longer duration than 
the pandemic of influenza, one of its years of greatest incidence being 
1923, at which time the influenza epidemic definitely had ceased. 
StriimpelF", who observed both the encephalitis accompanying the 
previous epidemics of influenza and the epidemic of lethargic encepha- 
litis, considered the two conditions to be distinct disease entities. This 
view was supported by Flexner^^ and is now generally accepted. The 
possible relationship of the influenza viruses^* to encephalitis will be 
discussed later. It is admitted by many^^' ^^' ^\ however, that an indirect 
relation may exist between influenza and encaphalitis in that an attack 
of influenza may so lower resistance as to permit the invasion of the 
body by the causative agent of encephalitis. 

Toxic theories of the origin of encephalitis, such as its relation to 
botulism^^ were investigated by the Medical Research Committee of the 
British Ministry of Health'^ They concluded that there was no relation 
between the two conditions. 

Much controversy has arisen regarding various bacteria, which have 
been isolated by a number of workers from cases of lethargic encepha- 
litis. The earliest of these reports was that of von Weisner^", who carried 
out the post-mortem studies on the first cases reported by von Economo. 

Vol. VI. 750 



82(2) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

The organism, which he isolated, a diplo-streptococcus, was accepted at 
first by von Economo as the causative agent, but later he considered it 
a saprophytic secondary invader^". 

Loewe, Strauss and Hirshfeld^\ using Noguchi's ascitic-fluid-kidney 
tissue media, cultured spinal fluids, nasopharyngeal washings, naso- 
pharynoreal mucous membrane and brain tissue from cases of encaphaiitis 
and reported that they obtained growths of minute globular bodies, 
occurring singly, in pairs, chains and clusters. The reaction to Gram 
stain was variable. The bodies would, with some difficulty, pass bacterial 
filters. Fifty per cent, of rabbits inoculated with these cultures suc- 
cumbed, showing lesions considered typical of encephalitis at autopsy. 
Flexner^® was unable to cultivate this organism under similar circum- 
stances and pointed out the frequency, approximately 50 per cent., of 
"spontaneous" encephalitis in the rabbit". This fact, the occurrence of 
spontaneous encephalitis infections in the rabbit, has rendered question- 
able much of the reported work on the causative agent of lethargic 
encephalitis. Apparently at least three types of such infections have 
been noted^^' "• ^^ In addition the possibility of the spontaneous occur- 
rence of herpes virus encephalitis in the rabbit still further complicates 
the picture. 

Rosenow in various experiments'*^' " has reported the isolation of 
streptococci with neurotropic tendencies from cases of lethargic enceph- 
alitis. In a later article*\ summarizing this work, he concludes, "the tenta- 
tive conclusion seems warranted that this organism has etiologic signifi- 
cance in each of the diseases studied". An evaluation of the possible 
etiological role of bacteria such as streptococcus viridans in encephalitis 
was made by AIcKinley". He considers the evidence for a bacterial 
origin of the disease to be highly doubtful. Zinsser^" has expressed similar 
opinions. 

The failure to recover bacteria regularly from the spinal fluid and 
tissues of cases of lethargic encephalitis and the resemblance of lethars^ic 
encephalitis, both in its clinical picture and its pathological lesions, to 
other diseases known to be produced by filterable viruses has given to 
the virus theory of its causation popularity above all others. 

A number of viruses, identical with or somewhat resemblmg the virus 
of herpes, have been found in cases of lethargic encephalitis by several 
workers. The first of these was isolated by Levaditi and Harvier'' in 
February, 1920. A patient, dying of encephalitis but also having facial 

Vol.' VI. 750 



LETHARGIC ENCEPHALITIS 82(3) 

herpes, was the source of the material used. A monkey and two rabbits 
were inoculated intracerebrally. The monkey and one rabbit remained 
SN'mptom free. The other rabbit became ill and died on the eighth day, 
the brain showing lesions similar to those of encephalitis. Later a second 
virus was obtained^- from material from the nasopharynx of another case 
inoculated upon the scarified cornea of a rabbit. A third virus was 
isolated and carried for a time''^ Together \\ith these successful isola- 
tions there were many failures to secure viruses from encephalitic 
material. 

Introduction of material from encephalitic patients into rabbits bv 
Kling and his coworkers^^ resulted in the reproduction of the picture 
of encephalitis. The nature of the causative agent and its possible relation 
to herpes virus and spontaneous encephalitis in rabbits has been the 
subject of some controversy^^ A later article indicated that this agent 
\\as not filterable. Koritschoner'*' and Kobavashi'^' have isolated viruses 
from cases of encephalitis considered by some to be tabic virus^^- ^^ 

Doerr and Vochting^" showed that encephalitis sometimes followed 
corneal implantation of herpes virus in rabbits. Blanc*'' believed that 
certain resemblances could be shown between the herpes virus and the 
virus isolated bv Levaditi. Other viruses probably of the herpetic group 
were isolated by Doerr and Schnabel"-. Doerr and SchnabeP^ and Leva- 
diti, Harvier and Nicolau"^ have studied further the similarities and 
differences bet^^Ten herpes virus and that isolated from cases of encepha- 
litis by Levaditi. 

The virus of Levaditi passes bacterial filters and is destroyed by 
antiseptics and bile. It is killed also by heat of ^^° C. Rabbits may be 
infected by inoculation intracerebrally or into the sciatic nerve. Also 
the scarified cornea or the anterior chamber of the eye, scarified skin or 
inflamed nasal mucous membrane and the testicles have been successful 
routes of inoculation. Very heavy doses given intraperitoneally or intra- 
muscularly occasionally produced infection. Intravenous, subcutaneous 
and intracutaneous inoculations most often were unsuccessful. In the sick 
animals the virus can be recovered from the brain and spinal cord, not 
from the spinal fluid or blood. The rabbit, guinea pig, monkey and 
mouse were susceptible to the virus. White rats, fowl and sheep were 
resistant. 

Virus neutralization tests with the serum of patients convalescent 
from encephalitis showed negative tests in five out of six cases. The one 
patient, who neutrahzed the virus, had had the acute phase of the disease 

Vol. VI. 750 



82(4) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

more than a year previoiislv- . Cross immunity tests showed that the virus 
ditfered from that of pohomyeUtis. 

Levaditi beheves that man is rather resistant to encephaUtis, requiring 
a lowered resistance to permit invasion of the nervous system by the 
virus. He also believes the herpes virus must acquire enhanced neuro- 
tropic characters before it can cause encephalitis. 

As a possible explanation of the numerous failures to secure the virus 
from encephalitic brain material Levaditi suggests that the brain may 
contain neutralizing bodies against the virus. He believes that the 
chances of isolating the virus are increased if the brain material is pre- 
served for a while in glycerin. Perdrau*'^ lends support to this theory. 

The low percentage of virus isolations, the fact that herpes virus has 
been found in the spinal fluid of cases not having encephalitis and finally 
the low incidence of positive virus neutralization tests in the serum of 
convalescent encephalitis patients are the chief obstacles to the accept- 
ance of the herpes-like viruses as the etiological agent of lethargic en- 
cephalitis. 

The occurrence of intranuclear inclusion bodies in known cases of 
herpes encephalitis in animals and in man'"' and their absence in lethargic 
encephalitis casts doubt on the identity of these two disease conditions. 

From this brief review it \\ ill be seen that the question of the causa- 
tive agent of lethargic encephalitis still awaits definite solution with the 
preponderance of evidence in favor of a virus perhaps related to that of 
herpes. 

Pathology 

The s^ross findings in the brain of cases of lethargic encephalitis 
usually are not striking^ The brain may appear entirely normal. There 
may be a slight hyperemia, a few small scattered hemorrhages, slight 
edema, rarely small areas of softening. Both von Economo'' and Stern^ 
lay stress on the paucity of the hemorrhagic phenomena considering this 
as being in distinct contrast with post-influenzal encephalitis. Micro- 
scopically perivascular infiltrations chiefly of lymphocytes, but with 
occasional small groups of polymorphonuclear leucocytes, are noted 
especially in the medulla, pons, the substantia nigra and other parts of 
the mid brain and the cerebral cortex. Some degenerative changes occur 
in the vessel walls. In cases of short duration areas of softening and 

Vol. VI. 750 



LETHARGIC ENCEPHALITIS 82(5) 

necrosis are rare and small. Some increase in glial cells is noted. Neu- 
ronophagia is, at most, slight in amount. Ganglion cell degeneration 
occurs in cases of considerable duration. These findings are typical of 
the acute stage of the disease. 

The findings in cases dying during the chronic stage of encephalitis 
are distinctly different. A case is reported by Stern\ autopsied six- 
months after the onset of encephalitis. Two months after onset this 
patient developed akinesia and marked hypertonic tremor with absence 
of spontaneous activity and marked weakness. Four months later death 
occurred from an intercurrent infection. At autopsy the brain showed 
practically no perivascular infiltrations or glial reaction. The chief 
lesions were located in the region of the subthalamus, lenticular nucleus 
and the substantia nigra and were in the nature of degenerative changes 
in ganglion cells with collections of pigment. Lipoid degeneration like- 
wise was noted in certain areas of the thalamus and hypothalamus. 

The other organs show few changes either in the acute or chronic 
stages of this disease. A terminal pneumonia is seen occasionally. Some 
fatty changes in the liver have been noted*'^ and in some cases a slight 
cirrhosis. Degenerative changes in the kidneys have been described also. 



Clinical Course 

The original description of von Economo^ covered most of the 
clinical features of the acute period of lethargic encephalitis. The disease 
sometimes is of sudden, sometimes of gradual onset. The initial symp- 
toms usually are headache and general malaise. Certain mild symptoms 
of meningeal irritation are seen often, but these ordinarily are not 
marked. A slight stiffness of the neck, a feeling of pressure in the eyeballs 
or a sensation of pounding in the head may be the chief manifestations. 
Occasionally a definite Kernig's sign is noted. After several days of 
symptoms such as these in the typical lethargic case somnolence develops. 
The eyes remain closed, and the patient sleeps continuously. From this 
sleep, however, the individual can be aroused and may answer questions 
quite rationally. Interspersed with the periods of sleep episodes of active 
delirium are likely to occur. 

The somnolence may deepen to stupor and coma, and death occur 
after a week or after a more prolonged course. Other cases may con- 
tinue to sleep for weeks or even months and then gradually lose their 

Vol. VI. 750 



82(6) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEM 

lethargy to recover or to pass over into some of the chronic sequelae of 
this disease. 

Fever occurs very irregularly in lethargic encephalitis. Usually an 
elevation of temperature of moderate degree occurs at least for a few 
days sometime during the course of the illness, but some cases apparently 
are entirely afebrile. No typical temperature curve can be described. 
Neither does the temperature bear any relation to the somnolence or 
delirium of the patient. 

Certain paralytic symptoms commonly occur. These are seen most 
often in the distribution of the cranial nerves but may be noted occasion- 
ally in the extremities. The nerves supplying the eye muscles are affected 
most frequently. Ptosis is common, beginning as a slight drooping of 
the lids, which the patient with some effort can overcome, and at times 
progressing to complete paralysis. Oculomotor palsies very frequently 
occur with paralysis of various external ocular muscles. Double vision 
is a very common symptom and may be the initial symptom of the illness. 
Other cranial nerves may be involved also with facial asymmetry, devia- 
tion of the tongue, difficulty in swallowing and hiccough as clinical 
manifestations. 

Evidences of visceral lesions during the acute stages in general are 
rare. Gastrointestinal symptoms are observed seldom. Occasionally 
abdominal pain occurs. Reys"^ believes that he has seen liver involvement 
with jaundice in the acute stage of encephalitis. Cardiac murmurs are 
quite uncommon. Some lowering of arterial tension is noted at times. 
The lungs occasionally may be the site of secondary infection, and a 
pneumonia may be the terminal event in either acute or chronic stages 
of encephalitis. Renal symptoms are rare. 

These clinical findings may be considered typical of the average case. 
It must, however, be pointed out that many cases present marked varia- 
tions from this typical disease picture. 

Regarding the regularity of occurrence of some of the common 
symptoms, the following illustrations may be given. Lethargy, the 
symptom from which von Economo originally derived the name of this 
form of encephalitis, is by no means universally found. According to 
Stern^ in loo cases there occurred outspoken somnolence in 41 per cent., 
transitory sleepiness in 9 per cent., dream states in 3 per cent., other 
drowsy or confused conditions in 14 per cent. In general about 40 per 
cent, show definite somnolence in all epidemics. 

Reversal of rest habits, sleeping during the day and restlessness at 
Vol.. VI. 750 



LETHARGIC ENCEPHALITIS 82(7) 

night, even marked insomnia, are quite common both in the acute stages 
and as a residual of this disease. Stern* states that as high as 20 per cent, 
may show these symptoms. 

Headache is the most common disturbance of sensation. It is present 
very frequently as an initial symptom and often persists during the acute 
stage. Pains in the muscles of the extremities and neck are common. 
Usually these disappear after the acute stage. Rarely they may pass over 
into chronic neuralgic pains. Headaches may persist also as a chronic 
symptom. Vertigo may be present in the acute or chronic stages of the 
disease. 

Paralysis of the eye muscles is quite frequent. Moritz noted pupillar)' 
disturbances in 75 per cent., nystagmus in 60 per cent., ptosis in 60 per 
cent., double vision in 40 per cent. Stern* in 200 cases from the literature 
found that 61 per cent, showed eye muscle disturbance. The same author 
found in 200 cases disturbances of cranial nerves other than those supply- 
ing the eye muscles in 50 instances, 25 per cent. Oculogyric crises, a 
peculiar intermittent spasm of the ocular muscles lasting from a few 
minutes to half an hour or more, are another common residual of lethar- 
gic encephalitis. This results in a conjugate deviation of the eyeballs 
usually upward but occasionally to one side or downward. 

The disturbances of the skeletal muscle system include marked gen- 
eralized lack of motor activity and loss of strength. Stern* considers that 
this may be due in part to a poor transmission of motor nerve impulses as 
well as to the generalized weakness usually accompanying infections. 
Certain irritative phenomena also are common as for example choreic 
movements and aimless tossing about; also rhythmic clonic movements 
and rhythmic muscular tremors and muscular twitching occur. These 
may be localized or general throughout the body. Rarely epileptiform 
convulsions occur. 

Stern* has described sev-eral important types of disturbances in mus- 
cular tonus. Three of the most important are akinetic hypertonia, spastic 
athetosis and chorea-like syndromes. These conditions frequently pass 
over into the full picture of parkinsonism. 



Laboratory Findings 

Occasionally albumin is found in the urine. The leucocyte count 
varies between 5,000 and 20,000 with an average close to 10,000. The 
differential count may be normal or show a slight increase in stab forms. 

Vol. \l. 750 



82(8) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

No constant changes in blood chemistry are noted other than those 
associated with dehydration. Slight increase in blood sugar accompany- 
ing increase in spinal liuid sugar has been noted occasionally. 1 he blood 
Wassermann reaction is not affected by this disease. 

The spinal fluid pressure in the acute stage is increased in many but 
not all cases. The fluid typically is water clear with little, if any, increase 
in protein content. Formation of a flbrin web and the occurrence of 
pigmentation of the fluid, while they have been reported, are rare*. 
Occurrence of hemorrhagic fluid probably is due in most instances to 
traumatism of vessels during the puncture since the nonhemorrhagic 
nature of the pathological process has been stressed. 

The leucocyte count in the spinal fluid is quite variable. Many 
observers have found entirely normal counts, others elevated counts. 
Stern* states that he has collected from the literature 490 cases, which 
showed an increased cell count during the acute stage, whereas 1 80 cases 
showed normal counts (see Table II). Usual counts are between 8 and 
17 cells per cubic millimeter. Of 258 cited by Merritt and Fremont- 
Smith"^ 117 had cell counts below 10 per cubic millimeter. Marked 
increases to levels between 100 and 500 cells are rare. No definite con- 
nection between cell counts and type of symptoms has been established. 
In the chronic stages of the disease, even one to two months after 
the onset, the cell count usually is normal. 

Regarding the types of leucocytes found in the spinal fluid, most 
observers find a preponderance of lymphocytes, although some observers, 
including von Economo, mention some cases in which the percentage 
of polymorphonuclear elements was increased. 

The chloride content of the spinal fluid usually is nomial. The 
g^lucose content of the spinal fluid sometimes is slightly increased, more 
often normal. Concentrations varying between 60 and 120 mgm. per 
100 c.c. usually are found. This serves as an important differential find- 
ing in separating encephalitis from bacterial infections of the cerebro- 
spinal system in which a definite decrease in sugar content is the usual 
occurrence. It does not difl^erentiate this type of encephalitis from the 
other virus infections of the central nervous system, since in these also 
the sugar content is not decreased. 

The colloidal gold reaction"** usually is negative but in some cases 
may show a midzone change, rarely even a first zone curve. The 
Wassermann test in the spinal fluid, as in the blood, is negative except 
in cases complicated by syphilis. 
Vol. VI. 750 



LETHARGIC ENCEPHALITIS 
Post-Encephalitic Parkinsonism 



82(9) 



The parkinsonian syndrome is one of the most common and dis- 
tressing sequels of the winter type of encephahtis. All authorities atjree 
that the incidence of this condition is quite high. Parsons"'' found "that 
parkinsonism followed encephalitis in 25 per cent, of 3, 112 cases which 
he collected from England, Scotland and Ireland. Ashie A4ain^" in a 
careful follow-up study of a series of Glasgow cases found 19.1 per cent, 
developed this sequel. Reys from Strasbourg" reported 40 per cent.. 
Stern 58.4 per cent, from Gottingen*. Howe in a series of cases in 



TABLE II - 


- Spinal Fi. 


uin Cf.li. Counts In 


Neurotropic \ 


IRUS 


Diseases 


Name of disease Ninnher 
of Cases 
Encephalitis lethargica 670 


I^ess than 
7 cells per 

cu. -111111. 

1X0 

(27%) 


7-2 fO 

cells per 

cu. mm. 

490 

(73%) 


2^1-1,000 1,001 to 
■ cells per cells per 
cu. vmi. cu. linn. 



Types of 
leucocytes 

found 
Nearly ioo% 
lymphocytes. 


St. Louis encephal 


itis 100 





94 

(94%) 


5 

(5%) 


I 
(1%) 




Nearly ioo°o 
lymphocytes. 


Lymphocytic 
choriomeningistis 


24 





(8%) 


10 

(42%) 


(50%) 




75° to 100°o 

lymphocytes. 


Eastern equine 
encephalomyelitis 


8 





2 

(25%) ( 


37-5%) (37-5%) 




Granulocytes 
may predom- 
inate in early 
stages. 


Western equine 
encephalomyelitis 


23 


Few 


Majority 
of cases; 
average 
130 celb 


\'ery 

few 







Adults above 
80^0 lympho- 
cytes, child- 
ren 50% gran- 
ulocytes. 


Poliomyelitis 


54 


I 

(2%) 


47 
(87%) 


5 

(9%) 


I 
(2%) 




Nearly 100% 
lymphocytes. 



children in the vicinity of Baltimore found 20 per cent, developed par- 
kinsonism". 

The syndrome consists of muscular rigidity, tremors, disturbances in 
gait and equilibrium and increased salivation. The rigor is generalized 
but perhaps most marked in the face''^ Due to rigidity of the masseters, 
there is difficulty in opening the mouth widely in mastication. In later 
stages difficulty in swallowing may develop. The face is mask-like, 
failing to show spontaneous movements and changes of expression with 
changes of emotions. The voice may be jerky, hurried, thick and monot- 

VoL. VI. 750 



8^10) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

onous. Retention of a spirit of vivacity far out of proportion to the 
lack of vivacity as indicated by the voice and facial expression is 

seen often. 

The increase in salivation causes the patient to swallow continuously 
to care for the excess saliva. Nevertheless, in many cases it may drool 
from the mouth. Next to the face, the neck may show the most marked 
rigidity. The two sides of the neck usually are involved equally, holding 
the head more or less immovable bur somewhat thrust forward and 
slightly flexed on the chest. Occasionally the involvement is not equal 
on both sides, and the head is rotated to one side or the other. The 
deep muscles of the neck ordinarily are more involved than the sterno- 
mastoid muscles. 

The trunk also takes part in the general muscular rigidity. This 
makes turnincj movements in walking a^'kward, exaggerated, angular 
and with many interruptions and pauses. Loss of normal associated 
movements contributes to this awkwardness. The normal swinging of 
the arms in walking frequently is lost, and the arms stay rigidly by the 
side. The rigidity of the lower limbs makes walking difficult and, to- 
gether with the fixed position of the head and trunk, so disturbs the 
center of cjraviry of the body as to lead to the type of locomotion 
characteristic of this condition. There is a running, staggering gait with 
the body somewhat bent forward. The center of gravity being too 
far to the front, the running gait appears necessary to prevent falling 
forward. With this there may be difficulty in maintaining equilibrium. 

The upper extremities often are less involved than other regions 
but usually show some degree of rigidity. With this there is also loss 
of ability to control the finer movements of the fingers, frequently made 
worse by the occurrence of tremors. 

In addition to their occurrence in the upper extremities, tremors may 
be noted in the face and lower extremities. These are typically fine 
tremors during repose but become coarse when movement is attempted. 

Increased secretion of sebaceous glands is noted often, giving the 
skin a peculiar greasy appearance. This may be accompanied by ex- 
cessive sweating. Alteration in vasomotor functions with low blood 
pressure, cold hands and feet are seen not uncommonly. Additional 
symptoms, sometimes noted, are difficulty in emptying the bladder and 
in moving the bowels. Urinary incontinence is rare, but retention is not 
uncommon. 

\'(!I.. \"1. 750 



LETHARGIC ENCEPHALITIS 82(11) 

Psychic Alterations 

In addition to the serious nervous residuals, just described, there are 
a number of psychic disturbances which are quite important. During 
the acute stages it has been noted that apathy and somnolence are quite 
common and may deepen into true coma. On the other hand, excitement 
and violent delirium may occur. 

As a residual of this disease mental retardation and nervous in- 
stability and alterations of personality are the most common and most 
important. Ashie Main'" has given a number of illustrative case reports 
of these residuals. 

Mental retardation is, of course, largely limited to cases which 
had their onset in childhood and is evidenced by failure of normal mental 
development in the period following the acute phase of the disease. 
There is dullness and failure to make normal progress in school. In a 
series of 70 cases, reviewed by Ashie Main'" five years after onset, 
mental retardation was noted in 2. In adults loss of memory and loss 
of power of mental concentration may be a counterpart of the mental 
dullness seen in children. 



Mental Instability 

Mental instability is defined by xAshie Main as a condition of marked 
restlessness and excitability, especially at night time. This also is seen 
mostly in children. Cases may show extreme emotionalism accompanied 
by whistling, singing, tossing and burrowing in bed, tearing the bed 
clothes until utterly spent. In these cases intelligence is good, and 
there is no lack of moral ideas, but mental instability is evident. Some 
of these cases later pass over into still more serious conditions. Ashie 
Main found five cases of this type in his series of 70, one year after the 
attack. When reexamined five years after the acute attacks one of these 
cases had died, one had developed perversion of conduct and three had 
developed parkinsonism. 

Nervous instability as a chronic residual manifests itself as insomnia, 
drowsiness and irritability. Such sequels are seen frequently in adults 
as well as children. Ashie Main'" found that 12 cases out of his series 
of 70 showed this type of disturbance five years after the acute attack. 
Insomnia is somewhat more common than drowsiness. 

Vol. VI. 750 



82(12) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

Alterations of personality and perversion of conduct is an extremely 
distressing residual of encephalitis. This may occur with or without 
symptoms of parkinsonism. The most common personality change is 
marked irritabilty. The individual develops a violent temper and is 
irritated and excited by incidents which prior to the attack of encephalitis 
would not have disturbed him. In some individuals, most of whom are 
children, the change amounts to complete perversion of conduct. These 
children may be impulsive, destructive and violent. They may lie and 
steal and show exaggerated erotic and sexual tendencies. While not 
feeble-minded in a technical sense, they may be mentally defective in 
respect to morals. Definitely criminal behavior may follow. The 
seriousness of the ultimate prognosis of lethargic encephalitis is well 
illustrated by referring again to the analysis of 70 cases by Ashie Main'". 
Incomplete recovery marked by such conditions as mental retardation, 
mental instability, nervous instability and physical defects were noted 
in 20 cases. A total of 18 cases developed definite parkinsonism, and 
of these eight also showed evidence of abnormal mental reactions. 
Twenty-one cases died; 18 of these terminated fatally between six days 
and five months after the onset. Three others died of parkinsonian 
complications between one and three years after the onset of encephalitis. 
Five cases were eliminated as of doubtful diagnosis. Seven cases only 
showed complete recovery after five years. 

Howe^^ has analyzed similarly a group of 66 children, who suffered 
attacks of encephalitis in the vicinity of Baltimore, Maryland. In this 
group 42 per cent, made complete recoveries after a five year period. 

Dimsdale'"'" in 1946 reviewed 320 cases of the parkinsonian syndrome 
and pointed out certain difference between those which followed a 
definite attack of encephalitis and those which had no history of 
encephalitis. One hundred cases were reviewed which occurred between 
1900 and 19 1 9 prior to the epidemic of lethargic encephalitis. Most of 
these developed symptoms between the ages of 5 1 and 60 years. The 
principal symptom and objective sign was tremor, most marked on 
the right side of the body. Abnormal mental states, ocular symptoms 
and excessive salivation were rare. One hundred additional cases were 
seen between the years 1920 and 1930. Thirty four of these resembled 
the previous group. Fifty four of this group followed shortly after a 
recognized attack of lethargic encephalitis. Shakiness Avas the most com- 
mon symptom, but muscular rigidity was marked on physical examina- 
tion. Mental symptoms and disorders of sleep, ocular symptoms and 

Vol. VI. 750 



LETHARGIC ENCEPHALITIS 82(13) 

excessive salivation were common. Eleven cases had symptoms re- 
sembling the postencephalitic group but had no history of an attack 
of encephalitis. One hundred and twenty cases were studied between 
193 1 and 1942. Fifty-two appeared to conform to the type of case 
seen in the years prior to 19 19. Twenty four had a history of an attack 
of encephalitis, although a long latent period usually was noted between 
the attack of encephalitis and the onset of parkinsonism. Forty-two cases 
appeared to resemble the post-encephalitic type but gave no definite 
history of encephalitis. Muscular rigidity was a marked feature of this 
group and the age distribution was such that they would have been 
young adults at the time when the epidemic of lethargic encephalitis 
was at its height. 



Differential Diagnosis 

The acute somnolent types of winter encephalitis can be confused 
with bacterial forms of meningitis as well as with lymphocytic chorio- 
meningitis, herpetic and post-infectional encephalitis, sporadic post-sea- 
sonal cases of St. Louis encephalitis, equine encephalomyelitis and 
encephalitic fomis of poliomyelitis. The points of value in differentia- 
tion are: 

1. Seasonal incidence; lethargic encephalitis is more common 
between December and May, while other types of encephalitis are 
more common in late summer and autumn. Lymphocytic chorio- 
meningitis occurs at any season. The post-infectional types of enceph- 
alitis have a seasonal distribution quite similar to that of lethargic 
encephalitis. 

2. Age incidence; winter encephalitis occurs at all ages but is 
most common in late childhood and early adult life. This contrasts with 
the encephalitic forms of poHomyelitis, which particularly attacks young 
children, and St. Louis encephalitis, which shows increasing incidence 
with advancing years. The post-infectious types of encephalitis are 
more common in relatively young children. Lymphocytic chorio- 
meningitis has about the same age incidence as lethargic encephalitis. 

3. Epidemiological distribution; lethargic encephalitis has a world- 
wide distribution but rarely with any great concentration of cases in a 
limited area. St. Louis encephalitis, like Japanese B encephalitis, shows 
sharply localized epidemics. Equine encephalomyelitis occurs, like St. 

Vol. VI. 750 



82(14) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

Louis encephalitis, in fairly well localized areas, often in association 
with that infection. 

4. Clinical course; in lethargic encephalitis there is an ill defined 
temperature change, which rarely is greatly elevated and has no relation 
to the severity of symptoms. The febrile reaction may be slight and 
of brief duration in cases in which the phase of somnolence and acute 
neurological symptoms may continue for many weeks or even months. 
This contrasts with the usual definite, febrile reaction of bacterial men- 
ingitis, the St. Louis type of encephalitis, equine encephalomyelitis and 
lymphocytic meningitis. As a rule, these diseases terminate in death or 
recovery in one to three weeks. In St. Louis encephalitis the severity of 
symptoms definitely runs more or less parallel with the severity of 
the fever. This is true also of the equine types of encephalomyelitis. 

Poliomyelitis has a brief initial fever and from then onw^ards usually 
is afebrile. The early onset of paralyses of the extremities serves to 
distinguish poliomyelitis from the encephalitis group of infections in 
most cases. 

Ocular and other cranial nerve palsies are much more common in 
lethargic encephalitis than in any other variety of encephalitis, although 
such palsies are present in a small percentage of cases of the St. Louis 
type. The persistence of cranial nerve palsies beyond the period of 
febrile reaction is much more typical of the lethargic type of encephalitis 
than of any other. 

The akinetic and hyperkinetic types of lethargic encephalitis, par- 
ticularly when they occur in afebrile cases and extend over a long period 
of time, are typical of lethargic encephalitis and very rare in any other 
type. The same is true of the occurrence of the parkinsonian syndrome 
either in the acute or chronic stages. The occurrence of serious, chronic, 
nervous residuals is far more common in lethargic encephalitis than in 
any other, except perhaps eastern equine encephalomyelitis, where in the 
few surviving cases severe residuals have occurred. 

The laboratory findings in the various forms of encephalitis and 
meningitis differ chiefly in the blood and spinal fluid findings. The 
peripheral blood in the purulent forms of bacterial meningitis shows 
usually a distinct polymorphonuclear leucocytosis. This is absent often 
in tuberculous meningitis. The various types of encephalitis, including 
lethargic encephalitis, show at most a mild leucocytosis, and often little 
change in the cellular elements of peripheral blood is found. 

Vol. VI. 750 



LETHARGIC ENCEPHALITIS 82(15) 

Purulent bacterial meningitis may show a positive blood culture. 
The blood culture in encephalitis is negative. 

The spinal fluid findings are of even greater diagnostic importance. 
In purulent bacterial types of meningitis the organism causing the infec- 
tion usually is demonstrable either by direct smear or by cultural 
methods. Even in tuberculous meningitis the tubercle bacillus may be 
demonstrated often. All of the viruses causing encephalitis are ultra- 
microscopic in size and will not grow on ordinary culture media. 

The examination of the cells of the spinal fluid is also of considerable 
diagnostic value. In lethargic encephalitis the spinal fluid often may 
show a normal cell count and usually shows less than 20 cells per cu. mm. 
Very high counts are rare. The average counts are lower than those of 
St. Louis encephalitis, equine encephalomyelitis and distinctly lower 
than that of lymphocytic meningitis. The other usual spinal fluid find- 
ings are a clear fluid with slight increase in pressure, slight protein 
increase, normal or somewhat high sugar content. The differential count 
of the cells of the spinal fluid shows chiefly lymphocytes. All of these 
findings occur in the other virus infections of the central nervous system. 
They do serve to differentiate this infection from purulent forms of 
meningitis in which the cell count is quite high, granulocytes predomi- 
nate in the differential count, and the spinal fluid sugar content and 
spinal fluid chlorides are reduced in quantity. It should be mentioned 
also that some cases of eastern equine encephalomyelitis show a pre- 
dominance of granulocytes in the spinal fluid. Tuberculous meningitis 
may show a lymphocytic pleocytosis in the spinal fluid in the early 
stages, but usually at least 20 per cent, of the cells are granulocytes''^ 

In the types of meningitis due to pyogenic bacteria the cell count in 
the spinal fluid usually is high, ordinarily above 1,000 per cu. mm., and 
the differential count shows a marked preponderance of granulocytes. 
The protein content of the spinal fluid is increased much more markedly 
in the bacterial types of meningitis than in the various forms of encepha- 
litis due to virus infection. The sugar content of the spinal fluid usually 
is normal or may be even slightly increased in encephalitis. In both tuber- 
culous meningitis and meningitis due to pyogenic bacteria the sugar 
content of the spinal fluid is definitely decreased except in the early 
stages of the disease. A similar difference is found in the chloride content 
of the spinal fluid. This remains near normal levels in the various forms 
of encephalitis, whereas usually it is definitely decreased in bacterial 
infections of the brain and meninges. 

Since the identity of the causative virus of lethargic encephalitis still 
Vol. VI. 750 



82 ( i6) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

is uncertain, it is not possible at this time to establish the diagnosis by 
virus isolation. Neither can we make use of virus neutralization tests or 
complement fixation tests to establish a positive diagnosis. These tests, 
however, can be used to exclude those types of virus infections which 
cause encephalitis and in which the causative virus is available. These 
tests are of value in excluding St. Louis encephalitis, the equine encepha- 
lomyelitis, lymphocytic meningitis and others. 



Treatment 

Because of the uncertainty of the identity of the causative agent in 
lethargic encephalitis little can be said regarding preventive measures. 
The rarity of any evidence of contagion has been noted by all students 
of the disease. The concentration of cases in a given area has seldom 
been such that drastic measures of isolation seemed indicated. The 
infrequency with which multiple cases occur in the same family suggests 
that spread may take place largely through healthy carriers. 



Specific TreatDieut 

In attempts at specific treatment a number of antibacterial sera and 
vaccines have been employed. NeaP" in 1942 reported the results of 
the extensive and careful work of the Matheson Commission on the 
treatment of lethargic encephalitis. Attention was given particularly to 
herpes virus, believed by Levaditi'^^ to be the causative agent of encepha- 
litis, and to the green-producing streptococcus, which Rosenow"' ^* and 
Evans and Freeman'^" believe to be the cause. 

Vaccines were prepared from the brain material of rabbits injected 
intracerebrally with herpes virus. Levaditi's strain "C" of herpes virus 
was used in the earlier work, but this virus soon lost its virulence. Later 
a strain of herpes virus, isolated by Perdrau, was used to test the immu- 
nity of rabbits previously^ inoculated with sublethal doses of a different 
strain of herpes virus. The vaccine prepared from the brains of the 
rabbits, which were found to be immune to the second herpes virus 
inoculation, was termed hyperimmune rabbit brain vaccine "X". These 
rabbits were also bled, and the hyperimmune serum was used in the treat- 
ment of a small numl)€r of patients with acute encephalitis. The serum 

Vol. \'^I. 750 



LETHARGIC ENCEPHALITIS 



82(17) 



treatments were soon discontinued on account of the occurrence of 
severe serum sickness. A third vaccine was prepared by Gay and Holden 
in 1933. This consisted of a formalinized herpes virus. 

A control series of cases received injections of normal rabbit brain. 
Alternate cases were treated for a time with Rosenow's streptococcus 
vaccine and injections of the rabbit brain vaccines. The herpes virus 
vaccine was given intramuscularly at daily intervals for the first few- 
weeks and then twice weekly until a total of 100 c.c. of vaccine had been 
given. 

The results with the herpes virus vaccines were much better than 
those secured with the Rosenow streptococcus vaccine. The formal- 
inized vaccine F appeared superior to the rabbit brain vaccine X. 

Cases treated with vaccine F and X showed a mortality in the acute 
stage of 1 1.8 per cent, compared to 24.6 per cent, in untreated cases. In 
the chronic stage untreated cases showed improvement in only 7.6 per 
cent, of the observed cases. When treated with the Rosenow strepto- 
coccus vaccine, only 4.5 per cent, were improved. With rabbit brain 
vaccine X improvement was seen in 16.9 per cent, of the chronic cases. 
A\'ith the formalinized herpes virus vaccine F 54.6 per cent, of the 
chronic cases treated from six months to five years showed improvement. 
This result with the fory/ialhiized herpes virus vaccine presents the most 
encouraging picture of any forni of treatment so far suggested for 
lethargic encephalitis. 



Chemotherapy 

Efforts at chemotherapy have included use of dyes such as acri- 
fiavine, trypaflavine and gentian violet and arsenicals, such as sodium 
cacodylate, arsphenamine, neoarsphenamine and tryparsamide. Various 
bismuth preparations and tartar emetic were tried. No definitely benefi- 
cial effects have been secured from any of these preparations. Yon 
Economo'^ has suggested the intravenous use of a 10 per cent solution 
of sodium iodide in doses up to 100 c.c. \\'ith this he also used urotropin 
(methenamine). 

The more recently developed antibiotics such as the sulfa drugs, 
penicillin and streptomycin have apparently no curative value in virus 
infections in o-eneral, and no effect has been reported in lethargic en- 
cephalitis. They can be of distinct value, however, in preventing and 
treating secondary bacterial infections which may occur as complica- 

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82 (1 8) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

rions of encephalitis. Good use can be made of these agents in treating 
complicating pneumonia and ascending infections of the urinary tract. 



General Measures 

Skillful and conscientious nursing care is an essential feature of the 
treatment of encephalitis. Particular attention must be given to measures 
which will insure adequate nutrition during the long periods of somno- 
lence in the acute stage and to the patients disabled by parkinsonism in 
the chronic stage. Administration of parenteral fluids and use of the 
nasal tube for feeding patients often are indicated. The diet must be 
adequate in all essentials including the vitamins. Attention must be given 
to the prevention of hypostatic pneumonia by frequent change of 
position as likewise to the prevention of decubitus. The disturbances 
in the nervous control of the urinary bladder and rectal sphincters, which 
are encountered sometimes, call for careful observation of the urine for 
evidence of ascending infection. 

Where spinal fluid pressure is found to be high, repeated spinal 
puncture or use of hypertonic glucose or surcrose solutions intravenously 
may be of value. 

Treatment of Nervous Sequelae 

After the acute phase of the illness has passed, the frequent occur- 
rence of the chronic nervous sequelae, particularly parkinsonism, has 
called urgently for tiie development of effective therapeutic aids. The 
experience of the last twenty years has led to the conclusion that deriva- 
tives of belledonna and stramonium are probably the most eff^ective 
agents at our disposal. Many physicians have used the pure alkaloids 
atropine and hyoscine. There is no question that a measure of relief 
from the symptoms of parkinsonism usually can be secured by the use 
of either or both of these alkaloids. 

An example of the method of use of atropijie is that of Kleemann'\ 
The alkaloid is administered in the form of 0.5 per cent, solution begin- 
ning with one minim (0.065 c-c.) twice daily and increasing by i minim 
(0.065 c.c.) twice daily until there is no further subjective or objective 
imnrovement. After continuing at this level for some time, the dose is 
reduced gradually until the first increase in unfavorable symptoms is 

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LETHARGIC ENCEPHALITIS 82(19) 

noted. When the most eifective dose has been determined, this is given 
in tablet form. 

Hyoscin also has been used widely. Its most effective dose also must 
be determined for each individual case, beginning with an initial dose of 
gr. 1/200 (0.3 mgm.) of the hydrobromide, two or three times daily. 

Apparently one of the most etfective of the treatments proposed for 
post-encephalitic parkinsonism is the ''Bulgarian treat'iiieiit^\ This con- 
sisted, in its original form, of a white wine decoction of the root of the 
Bulgarian belladonna plant. A Bulgarian apothecary, Ivan Raeff, was 
the first to make this preparation. The treatment was popularized in 
Italy by Panegrossi^^ and has now been used in many other countries. 
Neal"'' and Fabing^^ reported on its use in the United States. It is claimed 
that the effect of the total alkaloids of the Bulgarian belladonna root is 
superior to that of the pure alkaloids such as atropine and hyoscine. 
Most of those who have employed this treatment have been well im- 
pressed with its effectiveness. NeaP'^ believes that it probably offers the 
best available symptomatic treatment for postencephalitic nervous 
residuals. 

When used in the form of the decoction, the usual initial daily dose is 
2 to 3 c.c. (30 to 45 minims) given once daily. This is increased by i to 3 
c.c. (30-45 minims) daily until 20 c.c. (5 5) are reached. The daily dose 
then is divided and half given at 1 1 :oo A.M. and half at 11:00 P.M. The 
total daily dose then is increased until the most effective dose is reached, 
usually somewhere between 20 c.c. (05) and 60 c.c. (.32). Occasionally 
as much as 90 c.c. (5 3 ) has been given. 

The decoction of Bulgarian belladonna plant is said to contain an 
average of 0.2 mgm. of total alkaloids per cubic centimeter. The treat- 
ment has also been used in tablet form, each tablet containing 0.4 mgm. 
of total alkaloids. Starting with a single tablet, the dose is increased by 
one tablet daily until the best effect is secured. Dryness of the mouth, 
blurring of vision, dizziness, headaches, vomiting, diarrhea and difficulty 
in urination are symptoms of overdosage and call for halting the increase 
or decreasing the dose of the drug. The treatment is not recommended 
in the presence of hepatic, renal, myocardial or prostatic disease. Cases 
of idiopathic parkinsonism are said to tolerate this treatment poorly. 

Straiuoimim also has been used widely in the treatment of post- 
encephalitic parkinsonism". Treatment usually is administered in the 
form of the tincture, the extract or the dried leaves. Tolerance to this 
drug must be determined by gradually increasing the dosage in each case. 
Benzedrine sulfate is another drug w^iich has been used in the treat- 
VoL. VI. 750 



82 (2o) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

ment of parkinsonism. Favorable reports on its use have been published 
by Prinzmetal'', Davis and Stewart"' and Matthews*'^ Doses of 5 to 10 
mgm., once or twice daily, ordinarily have been employed, although 
doses as high as 30 mgm. occasionally have been given. 

Fever therapy has not been found to be effective in encephalitic 
parkinsonism. The same is true of various forms of shock therapy such 
as injections of foreign protein. 

Curare as d-tubocurarine in aqueous solution will relax temporarily 
the muscular spasticity of cases in the parkinsonian syndrome, but its 
action is so brief as to be of little value. The introduction of suspensions 
of d-tubocurarine in wax and peanut oil prolongs this action and offers 
another possible mode of treatment. Evaluation of this type of therapy 
requires further study. 

In June of 1948 Berger and Schwartz"^^ reported their studies on the 
oral use of a new drug ^'myaiieshf (3-ortho-toloxy-i, 2 propanediol) in 
conditions associated with muscular spasm. It had been used previously 
by parenteral injection, but the effect then is of brief duration. They 
administered the drug as a 3.3 per cent, (weight in volume) solution in 
20 per cent, (volume in volume) aqueous propylene glycol with syrup 
of cherry 20 per cent, (volume in volume) to improve the taste of the 
mixture. The usual single dose was 30 c.c. equivalent to i.o gram of 
"myanesin". Children were given proportionally smaller doses. These 
investigators felt that administration of this remedy in tablet or capsule 
form did not always give satisfactory absorption of the drug. Never- 
theless it is now usually administered as tablets. In parkinsonian syn- 
drome the oral administration of "myanesin" resulted in diminution of 
tremor and rigidity. More spectacular effects were seen after parenteral 
administration, but because of the brevity of action this mode of treat- 
ment did not seem practical. Oral administration gave a much more 
prolonged action and did not cause side effects. The best results were 
obtained if "myanesin" was given in addition to the usual drugs of the 
atropine type described above. Certain patients derived but little benefit 
from the medication. More experience is needed in the evaluation of 
this treatment, but it offers additional help in the management of this 
distressing condition. 

These are the chief medicinal measures, which have been found of 
some value in treatment of the nervous residuals of encephalitis. Many 
cases resist all forms of therapy, and in others only partial or temporary 
Vol. VI. 750 



HERPES SIMPLEX ENCEPHALITIS 82(21) 

relief is secured. For this reason in the following section possible surgrical 
mcvisures of treatment are described. 



Surgical Treatment of the Residuals of Encephalitis 

Many residuals of encephalitis are so disabling and distressing that 
the patients welcome the trial of surgical procedures which may promise 
relief. Reports of operations undertaken for this purpose describe some 
degree of success. Bucy and Case"- in 1939 reported relief of arm tremor 
resulting from traumatic injury by ablation of the contralateral arm 
area of the motor cortex. Klemme"^' "^ has reported a large number of 
cortical ablations for palsy, tremor and athetoid movements. In a series 
of 100 cases he reports that 39 patients were completely relieved and 
rehabilitated, 24 were relieved of signs and symptoms, but some evi- 
dences of inertia were still present. Fourteen cases were relieved except 
for reappearance of tremor under excitement. Six cases were complete 
failures, and there was an operative mortality of 17 per cent. Putnam"' 
succeeded in obtaining marked relief of unilateral tremor by section of 
the pyramidal tract at the level of the second cervical segment. The 
disability produced is less than that following cortical ablation in his 
opinion. Myerson and Berlin"'"" have reported relief of postencephalitic 
parkinsonism after total ablation of the thyroid gland. 



HERPES SIMPLEX ENCEPHALITIS 

In the discussion of lethargic encephalitis it was noted that viruses, 
which resemble or are identical with herpes virus, have been isolated 
from a number of human cases of encephalitis considered to be of the 
lethargic type. According to NeaP"' this was done in 14 instances prior 
to 1934. This represented a very small percentage of positive results 
considering the large number of cases in which such isolation had been 
attempted. For that reason the theory that lethargic encephalitis is 
caused by herpes virus can not be considered to be established. There 
is, however, recent evidence that the virus of herpes can cause an 
encephalitis in man. 

Smith, Lenette and Reams*^^ in 1941 reported the isolation of herpes 
simplex virils from the brain of a fatal human case of encephalitis. They 
were able to demonstrate intranuclear inclusion bodies in the brain tissue 

Vol. VI. 750 



82(22) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEAl 

similar to those seen in herpes encephahtis in the rabbit. A meningo- 
encephalitis with perivascular cellular infiltrations also was present. 

Two other more recent reports of herpes encephalitis are those of 
Zarafonetis, Smadel, Adams and Haymaker"^^ in 1944 and Whitman, 
Wall and Warren'" in 1946. In the latter case the examination of the 
brain showed areas of softening associated with loss of ganglion cells 
which had been replaced bv gitter cells. Special staining technique was 
required to bring out the acidophilic intranuclear inclusions. The orig- 
inal brain material yielded virus when inoculated into mice, guinea pigs 
and hamsters. When inoculated into chick embryos, it produced pock 
formation on the chorio-allantoic membrane, a phenomenon which the 
authors state is produced by no other neurotropic virus. 

Intranuclear inclusion bodies have not been a demonstrable finding 
in human lethargic encephalitis. It is noteworthy that the inoculation of 
herpes virus into Cebus monkeys produces an encephalitis resembling 
the lethars^ic type in man. Intranuclear inclusions are demonstrable in 
the early stages but not in the late stages of the disease in these animals^*^ 
The cases of human encephalitis, in which herpes virus and inclusion 
bodies have been demonstrated, have died in the acute stage of the 
disease. 

Herpes simplex encephalitis is now established as an infection which 
occurs in man. Its relation to lethargic encephalitis remains uncertain. 

The causative a^ent of herpes simplex belongs to the viruses of the 
genus Scehis and has been given the designation Scelns recurrens-^^ . It is 
the common cause of fever blisters in man. It has been transmitted 
successfully to rabbits, guinea pigs, white mice, cats, geese, hedgehogs 
and the chick embryo. It has a slight serological relationship to the virus 
of pseudo-rabies but none to vaccinia virus or to the known encephalitic 
viruses of the genus Erro^^^. 

No effective methods of prevention or treatment are available. 



POST-INFECTIOUS ENCEPHALITIS 

A number of the acute infectious diseases of virus or bacterial origin 
occasionally are followed by encephalitis. Influenza'''^ measles'®' and 
German measles'®^ mumps"'^ variola'"", vaccinia'^', varicella'", infectious 
mononucleosis-"** and pertussis'^''- '^^ are all infections following which 
encephalitis has occurred. While the seasonal incidence of these infec- 

VOL. VI. 7^0 



POST-INFLUENZAL ENCEPHALITIS 82(23) 

tions is somewhat variable, they occur most commonly in the late fall, 
winter and early spring. 

The encephalitis observed following these infections is characterized 
by a marked similarity in clinical symptoms and also in the pathological 
lesions produced in the nervous system. There is no direct evidence that 
the viral agents, which cause a number of these infections, are operative 
in producing the encephalitis which follows, although this possibility 
can not be ruled out. Some believe that the antecedent acute infection 
may lower resistance to an as yet undiscovered neurotropic virus which 
is the actual cause of the encephalitis. It is a curious fact that encephalitis 
following these infections, other than jnfluenza and perhaps mumps, was 
mentioned seldom prior to 19 18, suggesting that the occurrence of the 
pandemic of lethargic encephalitis possibly may have influenced the 
appearance of this form of encephalitis. However, the pathological 
picture seen in these cases differs from that of lethargic encephalitis. 
Some regard post-infectious encephalitis to be the result of a toxin or an 
allergic reaction to the infecting agent. In the case of the nervous symp- 
toms following whooping cough there is evidence that the hemorrhages 
in the brain, following the violent paroxysms of coughing, may be, in 
part, responsible. 

The pathological picture which is common to the entire group is 
characterized by congestion and multiple small hemorrhages and by the 
occurrence of perivascular areas of demyelination particularly in the 
white matter. Perivascular lymphocytic infiltrations occur only occa- 
sionally, and destruction of nen^e cells is not a prominent feature. 
Numerous vascular lesions are noted including sweUing and hyperplasia 
of the endothelium and extensive thrombi. These may account for some 
of the nervous symptoms'"'- "^- '"• "^ 

Some cases, presenting this pathological picture, have occurred with- 
out recognizable antecedent acute infections. To these the designation 
of acute disseminated encephalomyelitis has been given. Some of these 
cases may closely resemble multiple sclerosis'"^' "I 



Posr-INFLUENZAL ENCEPHALITIS 

The occurrence of cases presenting the clinical picture of enceph- 
alitis more or less in association with epidemics of influenza has been 
recorded for many years. During the influenza epidemic of 1889- 1890 
Pfuhl and Leichtenstern' described a type of hemorrhagic encephalitis 

Vol. VI. 750 



82(24) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

which they beHeved to be due to influenza. Ebstein^ about the same 
time described another group of cases to which the name, "nona", has 
been given. These also had symptoms suggestive of infection of the 
central nervous system. 

In 1909 Hassin'"'^ described 4 cases of hemorrhagic encephalitis, 3 
of which were preceded by an attack of influenza. He states that most 
authors have found that some time elapses between the recovery from 
influenza and the onset of the symptoms of encephalitis. This interval 
may be days, weeks and even months. 

Toward the end of World War I the pandemic disease which became 
known as "lethargic encephalitis" made its appearance in Europe, As 
already stated in this text, the first cases probably were observed in 
Rumania^ in 19 15. A number of additional cases occurred in France^ 
in 191 6, and in 191 7 von Economo"' gave his classical description of this 
disease based on cases which he observed in Vienna during the winter 
of 1916-1917. In this first publication von Economo felt it necessary 
to raise the question whether these cases, which he was observing, could 
be cases of influenzal encephalitis. He offers as evidence against this 
idea that there was no unusual prevalence of influenza in Vienna at the 
time, and that the pathological picture in the brain in cases of lethargic 
encephalitis did not show the hemorrhagic lesions described by Pfuhl 
and Leichtenstern. The great influenza epidemic did not occur until 
at least a year later. 

In the United States lethargic encephalitis and the 191 8 pandemic 
of influenza made their appearance about the same time. However, the 
last wave of the pandemic of influenza was over by the spring of 1920, 
whereas the peak of the cases of lethargic encephalitis was not reached 
until the year 1923, and the disease continued with high prevalence for 
a number of years thereafter. Hurst'**" made an extensive study of the 
statistics of the two diseases and came to the conclusion that there was 
no parallelism in the outbreaks of these two infections. 

In 1930 Greenfield'"^ described an acute disseminated myelitis as a 
sequel to influenza. The pathological lesions in the two cases, which 
he described, were characterized particularly by demyelination and 
resembled the findings in cases of encephalomyelitis which have fol- 
lowed vaccination, smallpox and measles. 

Viruses, known to be the causative agents of influenza, have now 
been isolated'^ and occur in several serologically distinct types. They 
cause pathological lesions, when inoculated into ferrets, mice and 

Vol. VI. 750 



POST-INFLUENZ AL ENCEPHALITIS 82(25) 

hamsters. They can cultivated readily in eggs and have the property 
of agglutinating chicken erythrocytes"''. 

Neal and Wilcox''^ in 1937 reported observations on a number of 
cases in which an acute respiratory infection diagnosed as "grippe" had 
been followed by development of various neurological conditions. In 
16 such instances the serum of the patients obtained from one to four 
months after the respiratory infection failed to show the presence of 
influenzal antibodies in 14 and only very weak antibodies in the other 
2 cases. 

In 1945 Broun, Muether, Pinkerton and LeGier"- reported observa- 
tions on a case of encephalitis which followed a respiratory infection 
at a time when influenza was prevalent. A high titre of influenza anti- 
bodies was found in this case. Spinal fluid from this patient was inocu- 
lated into chicken eggs. The chorioallantoic fluid of these eggs gave 
a weak positive agglutination to chicken erythrocytes. This reaction 
became stronger in subseqent transfers. After a number of transplanta- 
tions in eggs the chorioallantoic fluid was inoculated intranasally and 
intracerebrally into mice with the production in a large percentage of 
animals of pneumonia and mild encephalitis. Several successful mouse 
passages were made, but later the virus was lost. Serological tests of 
this virus by the antihemagglutinin test of Hirst"" with known influenza 
virus antiserum type A and type B failed to indicate serological relation- 
ship with these strains of influenza virus. The patient's own serum in- 
hibited the agglutination of chicken cells by this agent in a dilution of 
1/250. The identity of the infecting agent was not established, and 
the possibility that it was a virus occurring spontaneously in mice can 
not be excluded. During these studies it was noted that intracerebral 
injection of mice with the Pr 8 strain of influenza virus produced a mild 
encephalitis. This fact has been reported also by Henle and Henle'*^ 

Proof of the existence of true influenza encephalitis in man can not 
been established until typical viruses of the influenza group are isolated 
from human brain material of a definite case of encephalitis. This, so 
far, has not been accomplished. 

In addition to the question of the occurrence of cases of encephalitis 
caused by influenza virus there is also the possibility that an infection 
with the virus of influenza may lower the resistance of the body so as 
to allow invasion by some other virus with neurotropic properties. 
Many believe in the existence of this relationship between influenza 

Vol. VI. 750 



82(26) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEM 

and encephalitis who question tlie occurrence of encephalitis due to the 
influenza virus itself. 

ENCEPHALins Following Measles 

Symptoms suggesting encephalitis probably occur more frequently 
following measles than any other of the common exanthemata of the 
childhood period. Typical cases of this condition have been reported 
more frequently in recent years than in the years prior to 191 8. How- 
ever the 191 6 edition of Osier and McCrae's, Text Book of Medicine^" 
notes among the neurological complications of measles, hemiplegia, para- 
plegia, acute mania, "meningitis" and multiple sclerosis. 

Ford'**"* notes that neurological complications occur in 0.4 per cent, of 
all cases of measles. He distinguishes syndromes indicating diffuse cere- 
bral involvement, multiple focal or diffuse lesions, single focal lesions, 
cerebellar syndromes, spinal syndromes and optic neuritis. Nervous 
symptoms make their appearance usually on the fourth to the sixth day 
of the course of measles after the rash has begun to fade. Occasionally, 
as in a case described by Malamud^"^ the nervous symptoms may precede 
the appearance of the rash. Neal and Harrington^'^ describe measles 
encephalitis as of sudden onset, accompanied by fever, headache and 
stiff^ness of the neck. Convulsions, vomiting and muscular twitching 
also are common symptoms. Usually the mental condition of the patient 
is somewhat disturbed, varying from mild irritability or apathy to marked 
drowsiness, stupor or delirium. Paralyses or pareses are seen involving 
cranial nerves or those of the trunk or extremities. Diplopia was ob- 
served in two instances. The paralyses may be spastic or flaccid. Super- 
ficial and deep reflexes were variable throughout the illness, more often 
diminished than hyperactive. About one half of the patients showed 
positive toe signs at some time during the course of tlic encephalitis. 
Inequality of pupils with sluggish reactions occasionally are observed. 
Temporary blindness sometimes occurs. The duration of the illness is 
quite variable lasting from two weeks to several months. 

Spinal fluid examination shows, as a rule, some increase in pressure 
with a slight rise in the cell count to levels usually less than 100 per 
cu. mm., although in one instance a cell count of 540 was observcd''\ 
Lymphocytes and mononuclears predominate. Protein content is nor- 
mal or slightly increased. Sugar is normal or high. The peripheral 
blood usually shows a moderate polymorphonuclear leucocytosis. 

Vol.. VI. 750 



ENCEPHALITIS FOLLOWING VARIOLA 82(27) 

According to Ford'*^ the mortality is about 10 per cent. Nearly 
two-thirds of those who survive show some residuals such as weakness 
in 30 per cent., ataxia in 12 per cent., mental and personality defect in 
12 per cent, and epilepsy in 5 per cent. Neal and Harrington^'^ observed 
a mortality of 13.5 per cent. Of the survivors 73 per cent, made com- 
plete recoveries. Twenty-seven per cent, showed a variety of residuals 
of greater or lesser severity. 

Immune globulin, which is of some value in measles, so far has not 
been reported as of value in post-measles encephalitis. Unless this proves 
of some value, treatment is entirely symptomatic. 

German Measles Encephalitis 

Serious nervous symptoms following German measles were reported 
very rarely prior to 1934. Headache and rigidity of the neck frequently 
have been noted at the onset when lymph nodes at the base of the skull 
often become greatly enlarged. After the year 1934 a number of 
cases of encephalitis following this infection were seen in various parts 
of the United States^*'^' ''*' '''■ '''■ ''\ 

The clinical picture is marked by sudden onset of fever, headache, 
neck rigidity, drowsiness, convulsions, coma, muscular tremor and at 
times, ataxia. The spinal fluid shows a variable cell count, with lympho- 
cytes usually predominating, although NeaP'^ has observed a case in 
which polymorphonuclears were in the majority. The total number of 
reported cases is small, and these include 5 fatal cases, so that the mor- 
tality would appear high. Little is known concerning residuals. No 
specific treatment is available. 

Encephalitis Following Variola (Small Pox) 

Encephalitis as a complication of variola (small pox) apparently is 
quite rare. The most extensive studies of this condition have been pub- 
lished in England. RoUeston^*^ and Marsden and Hurst"*' describe an 
encephalomyelitis with onset usually between the fifth and thirteenth 
day after the appearance of the rash. The chief symptoms are headache 
and drowsiness, irritability and an unsteady gait. Nausea and vomiting 
sometimes occurred with salivation and marked sweating. Spinal and 
cranial nerves may be involved. Rice and Carey^''" report a case from 
the United States with hemiplegia. 

\^oL. VI. 750 



82 (:8) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEM 

Examination of the spinal fluid in the cases of Marsden and Hurst^^® 
showed a pleocytosis of from lo to 500 cells per cu. m.m. of which half 
may be granulocytes in the early stages of the encephalitis. Later lymph- 
ocytes only were found. A number of deaths occurred. The pathology 
of this condition has been described by Finley^'" as well as by Marsden 
and Hurst^'^ 

Post- Vaccinal Encephalitis 

Prior to the appearance of the pandemic of lethargic encephalitis 
following \\^orld ^^'ar I cases of encephalitis associated with vaccination 
against small pox very rarely w^re reported. In the ten year period 
betw^een 1924 and 1934 these cases became sufficiently numerous to 
attract attention. Comby^"", Lucksch"'-, Bastiaanse^"^ and TurnbuU and 
Mclntosh'^^ contributed to our knowledge of this condition. There 
appears to have been a decline in cases of post-vaccinal encephalitis in 
recent years coincident with the decline in lethargic encephalitis. 

Several theories regarding the origin of this form of encephalitis 
have been offered: 

(i) That it is due to the vaccinia virus itself, this virus having de- 
veloped neurotropic properties in such cases. The increase coincident 
with the epidemic of lethargic encephalitis would in this case be ex- 
plained by better recognition of all types of encephalitis due to the 
greater interest of physicians in this group of diseases at this time. 

(2) That some other neuroptropic virus was activated by the vac- 
cinal infection, and a symbiotic action of the two viruses accounts for 
the encephalitis. The neurotropic virus, activated in this manner, might 
be a single agent and might even be the virus of lethargic encephalitis 
itself. 

(3) Post-vaccinal encephalitis may represent an allergic reaction to 
vaccination. This theory would seem to infer that the cerebral vascular 
lesions may occur as a result of pathological changes analogous to the 
periarteritis nodosa which may follow serum injections. Rivers'^^ sug- 
gests that the vaccinal virus lesions in the skin might release antigens, 
which would particularly affect other structures of ectodermal origin 
such as the brain. 

In regard to the direct causation of encephalitis by vaccine virus 
there are a number of studies in which the effect of intracerebral inocu- 
lations of this virus in animals was noted. The results are quite variable, 

\''oL. VI. 750 



POST- VACCINAL ENCEPHALITIS 82(29) 

Gordon^*'' and Mcintosh'^' believed that they were able to produce 
encephalitis by inoculation of vaccinia virus. Ikei"^*^ was not able to 
produce encephalitis unless the animal was subjected also to excessive 
heat or trauma. Bouman'" and Matsuda^"^ could not produce enceph- 
alitis in animals by vaccinia virus inocluations. The positive results were 
obtained many times in rabbits which are subject to spontaneous en- 
cephalitis after various experimental inoculations. 



Pathology 

The pathology of post-vaccinal encephalitis has been described by 
Turnbull and Mclntosh^-'^ and by Mcintosh and ScarfT"'. They describe 
widely disseminated lesions both in the brain and the cord involving 
both the grey and white matter without any sharp localization of lesions. 
Little meningeal involvement was noted. Marked demyelinization was 
present with perivascular infiltrations spreading out into the surroundino- 
parenchyma. Some vessels showed hyalin thrombi with some endothelial 
proliferation. Few hemorrhages were seen. In the exudate were many 
large endothelial cells with clear oval nuclei together with a few lymph- 
ocytes and polymorphs. Plasma cells were found rarely. 

Perdrau""" in his study of the pathology of this condition also de- 
scribed the perivascular areas of demyelinization and expressed his belief 
in the histological identity of the lesions with those seen in the enceph- 
alitis following the Pasteur treatment of rabies, following measles, small 
pox and other acute fevers as well as points of similarity to multiple 
sclerosis. Finley^^^ also stresses the similarity bet\\-een these types of 
encephalitis. He pointed out the similarity also in the incubation period 
in these various forms of encephalitis averaging about 1 1 days. 

Ojiset and CVmical Course 

Encephalitis following vaccination need not have been preceded 
by a severe reaction to the vaccination itself. The neurological symp- 
toms may appear as early as the 2nd and as late as the 25th day after 
the inoculation, but with most cases the onset is between the ninth and 
fifteenth day. The onset mav be abrupt or gradual. Convulsions are 
seen fairly conmionly. Somnolence, apathy and stupor occur in most 
cases with some signs of meningeal irritation. Some alteration of the 
deep reflexes with pathological toe signs often are observed. Peripheral 

Vol. VI. 750 



82(30) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

muscle palsies occasionally occur together with muscle twitching and 
tremors. Sensory changes are rare. The spinal jfluid may be normal, 
but frequently some increase in pressure and moderate pleocytosis are 
noted. In e^eneral, it is not easy to distinguish the clinical findings from 
those of epidemic encephalitis or the encephalitis following measles. 

Persistent nervous residuals occur in some cases. NeaP'^ describes 
as residuals, nervousness, stammering, muscular atrophy and contrac- 
ture and lo^vered intelligence quotient. These resemble the residuals 
of lethargic encephalitis. 

The mortality in this type of encephalitis has been between 30 per 
cent, and 50 per cent. 

Since no specific treatineiit is known the management of each case 
is on a symptomatic basis. 

Encephalitis Following Chicken Pox 

The older literature makes little reference to neurological complica- 
tions following varicella. Osier's 19 16 edition of his Textbook of Aledi- 
cine^" mentions hemiplegia as a rare complication. More recently case 
reports of encephalitis following this disease are appearing with increas- 
ing frequency. Underwood'"'" collected 119 cases from the literature 
up to 1935 ^^^^^^ '^ mortality of 10 per cent, and with the occurrence of 
ciironic residuals in 12.6 per cent. Bullowa and Wishik""^ reported that 
encephalitis occurred as a complication in 5 instances in 2,534 cases of 
varicella seen between the years 1929 and 1933, an incidence of 0.2 per 
cent. Neal^'^ and Lowry-"^ also have reported observations on this con- 
dition. 

The onset usually is two to eight days after the appearance of the 
rash and occurs suddenly. Fever, headache, vomiting and stiffness of 
the neck are the most constant symptoms. Somnolence, apathy, stupor 
or irritability were present in most cases. Irregular changes in the deep 
and superficial reflexes were noted. Strabismus, nystagmus and blurring 
of vision occasionally occurred. Hemiplegia and paralyses of the ex- 
tremities occur rarely. 

The spinal fluid showed an increased cell count \\ hich was often 
above 500 per cu. ulul with mononuclear cells predominating. The 
extremes of the counts noted were as low as 15 per cu. m.m. to as high 
as 2,795 per cu. m.m. In the case with the higlicst count 85 per cent, 
of the cells seen were polymorplionuclears. 

Vol. VI. 750 



ENCEPHALITIS FOLLOWING MUMPS 82(31) 

The residuals noted are similar to those seen after encephahtis due 
to measles. No preventive measures are available and there is no spe- 
cific treatment. 



ENCEPHALITIS FOLLOWING MUMPS 

The identification of the causative agent of mumps as a filterable 
virus was reported by Johnson and Goodpasture-"' in 1934. The fact 
that neurological symptoms often are noted in association with this 
infection had been recorded at a much earlier date^", Holden, Eagles and 
Stevens-"" studied 100 consecutive cases of mumps admitted to the A.ST. 
Regional Hospital at Fort Benning, Ga. Of these 3 3 showed clinical signs 
of meningoencephalitis. Ten additional cases were found to have 
changes in the spinal fiuid, pleocytosis and increased protein, without 
clinical symptoms of involvement of the central nervous system. The 
meningoencephalitis following mumps is believed by many to be due 
to the causative virus of mumps itself^*'. Nevertheless, as in the case of 
other postinfectious types of encephalitis, the possibiUty that this virus 
infection merely lowers resistance against the invasion of some other 
neurotropic virus can not be excluded. The author has seen a rising titre 
of virus neutralizing antibodies against the virus of St. Louis encephalitis 
during the convalescent period of a case of encephalitis which developed 
during an attack of mumps. 

Kane, Enders, Cohen and Levens"" have developed a complement 
fixation test as an aid in the diagnosis of this condition. They found that 
complement fixing antibodies appear 8 to 14 days after experimental 
inoculation in monkeys. In a study of 51 cases of "aseptic meningitis" 
thev noted complement fixing antibodies against mumps virus in approxi- 
mately two thirds of their cases. One third of their cases had had a 
recent attack of parotitis. One third had antibodies against mumps virus 
without a previous history of an attack of mumps. This suggests that 
mumps virus may possibly cause an aseptic meningitis in some cases 
without giving rise to parotitis. 

While mumps may appear at any season, most outbreaks of this 
disease are noted between December and the end of June. In the cases 
of aseptic meningitis studied by Kane and Enders""^ 94 per cent, of those 
associated with parotitis occurred in the first seven months of the year. 
Of the cases giving positive complement fixation tests without parotitis 
73 per cent, occurred in the first seven months of the year. The cases 
Vol. VT 750 



V,i{iz) EXCEPIIALI US AND O IHER \1RUS INFECTIONS 
OF FHE CENTRAL NERX'OUS SYSTEM 

giving negative complement fixation tests for mumps virus mostly oc- 
curred in the warmer months of late summer and early autumn. 

1 he chief clinical symptoms of mumps meningoencephalitis""^ are 
headache, drowsiness and neck rigidity. The leucocyte count in the 
peripheral blood varies between 4,000 and 12,000 per cu. m.m. with the 
majority falling between 5,000 and 6,000. The spinal fluid cell count 
is somewhat elevated in nearly all cases and may be as high as 900 per cu. 
m.m. 1 he cells found are mostly lymphocytes. Spinal fluid protein is 
elevated in about one fourth of all cases. There is no relationship be- 
tween the severity of the parotitis and the severity of the meningo- 
encephalitis. 

Compared to other types of post-infectious encephalitis such as those 
following measles, rubella and varicella, the symptoms usually are milder, 
chronic residuals are rare, and the mortality is very low. Osier and 
McCrae^" state that the Index Catalogue of the Surgeon General's Office 
contains reports of 5 fatal cases up to 19 16. A fatal case was reported 
by Larkin^"'"' in 1920. The autopsy showed congestion of the pia arach- 
noid, slight distention of the ventricles and microscopically perivascular 
collections of large and small mononuclear cells in the pia arachnoid 
extending into the cortex. 

ENCEPHALITIS ACCOMPANYING INFECTIOUS 
MONONUCLEOSIS 

it 

The occurrence of symptoms of central nervous system involvement 
in cases of infectious mononucleosis has been recognized since the reports 
of Johansen"'"* and of Epstein and Dameshelr"" in 193 i. Since the cause 
of infectious mononucleosis remains obscure, it is uncertain whether this 
is a vims infection of the nervous system. It is also uncertain \\ hether 
the nervous lesions are due to the causative agent of infectious mononu- 
cleosis or represent a complicating infection. The onset of the nervous 
symptoms may precede or follow the appearance of the typical blood 
changes of this disease. The author has had an opportunity to observe 
a number of cases suff^ering from this condition. One case, which began 
with a picture of encephalitis and raised a problem in differential diag- 
nosis, occurred in St. Louis in August 1937 during the second epidennc 
of St. Louis encephalitis. A white female, 20 years of age, was taken ill 
suddenly with severe headache, a temperature of 104° F., drowsiness and 
marked neck rigidity. The leucocyte count at the onset was low with 
\'oL. \'I. 750 



ENCEPHALITIS FOLLOWING WHOOPING COUGH 82(33) 

a preponderance of granulocytes but soon shifted to a picture of mod- 
erate leucocytosis, and the differential showed a higrh percentas^e of 
lymphocytes and monocytes of the types seen commonly in infectious 
mononucleosis. The titre of heterophile antibodies against sheep cells 
rose to 1:1,250. The serum was tested also for neutralizing antibodies 
against St. Louis encephalitis virus. None were found during the conva- 
lescent period. This patient made a rapid and complete recovery. The 
examination of the spinal fluid during the height of the illness showed a 
normal cell count and no elevation of spinal fluid protein. Several similar 
cases have been seen during the cooler months of the year when St. Louis 
encephalitis was not prevalent. A slight increase in lymphocytes in the 
spinal fluid was found sometimes as well as some increase in protein. 

Recent reports of the central nervous system symptoms of infectious 
mononucleosis are those of Geliebter"^" and Slade"". The latter gives 
an excellent review of the literature and decribes the clinical features of 
this condition. Fever, headache, somnolence and neck rigidity together 
with a slight lymphocytic pleocytosis in the spinal fluid are the most 
common findings. The nervous manifestations are quite varied, and 
evidences of spinal as well as meningeal and cerebral involvement may 
be seen. 

While most of the reported cases have recovered without serious 
residuals, Slade"" reports two cases in which the effects were sufficiently 
severe to require the permanent separation of soldiers from military 
service. The author recently had an opportunity to see a case under the 
care of Dr. W. L. Aloore of St. Louis in which respiratory paralysis 
occurred. This has been the cause of death in at least four cases reported 
by Thomsen and A^imtrup"'". Ricker, Blumberg, Peters and \\'iderman^^^ 
also have reported a fatal case due to ascending paralysis. Like other 
types of post-infectious encephalitis, that accompanying mononucleosis 
may cause a fatal outcome in a disease usually considered to be quite 
benign. 

ENCEPHALITIS FOLLOWING W^HOOPING COUGH 

Convulsions occur quite frequently in whooping cough but are 
believed by Habel and Lucchesi"'* to be due to cerebral anoxia and hence 
do not necessarily indicate the presence of encephalitis. NeaP" has 
reported observations on 16 cases considered as having developed en- 
cephalitis as a complication of pertussis. Convulsions, somnolence, stupor 
and apathy were common features in these cases. Variable chanq'es in 

Vol. VI. 750 



82(34) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NERX'OUS SYSTEM 

the pupillary reactions and reflexes were noted. The spinal fluid showed 
a slight to moderate Ivmphocvtic pleocvtosis. This fluid was sometimes 
bloody. At least one case developed chronic nervous residuals, and there 
were 3 deaths in the series of 1 6 cases. 

Since whoopingr couijh is considered to be of bacterial origin, we 
would have to consider the encephalitis to be a complicating infection, 
if we wish to classify this type of encephalitis among those due to viruses. 



Vol. VI. 750 



RUSSIAN SPRING-SUMMER ENCEPHALITIS 82(35) 

GROUP II. 

Types of Encephalitis Occurring Chiefly in 
Late Spring and Early Summer 

RUSSIAN SPRING-SUMiMER TICK-BORNE ENCEPHALITIS 
(FOREST SPRING ENCEPHALITIS) 

Definition. — Russian spring-summer tick-borne encephalitis may be 
defined as an acute infectious disease occurring in the late spring and 
early summer months, caused by a filterable virus and transmitted by the 
bite of a tick, characterized by lesions of the brain and spinal cord, which 
frequently result in pareses and paralyses of the limbs, neck and back 
with subsequent atrophy of the affected musculature. 

Historical Account 

According to Smorodintseff"^' a clinical description of cases of this 
disease was given by Prof. Pervushin of Perm about 1900. Cases were 
described in the Ural Mountains in 19 14 and in the Far East in 192 i and 
1923. The disease was intensively studied and its etiology and epidemi- 
ology clarified through the work of Olshenskaya, Levkovich, Silber, 
Pavlovsky and Smorodintseff and their associates"'^ during the years 1937 
to 1939. 

Geographical Distribution 

This form of encephalitis has been recognized in various parts of the 
U.S.S.R. including the Far East, Siberia, the Ural Mountains and Euro- 
pean Russia. Beyond the limits of the Soviet Union it has not been 
described. 

Incidence 

This type of encephalitis has a pronounced seasonal character. Cases 
begin to appear by the end of April and gradually increase in number 
to reach a peak in the last ten days of May and the first ten days of June. 
Seasonal temperatures usually are moderate and humidity is relatively 
high at this time of the year. 

Vol. VI. 750 



82(36) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\'OUS SYSTEM 

Children up to five years of age are seldom infected. Young adult 
males are affected most frequently. Old men and women are less sus- 
ceptible to the disease. 

The disease occurs almost exclusively in uncultivated and slightly 
cultivated forest areas, particularly in newly established communities. 
Only those are affected who live and work in the woodlands or come in 
contact with them. The great majority of cases occur in lumbermen, 
surveyors, road-builders, hunters, geologists, etc. 

Epidemiology 

There is little evidence of contact transmission. The disease appears 
widely dispersed through vast forest areas at a time of the year when 
contact between the forest workers is limited. Sick patients do not 
transmit the disease to others in their homes. Cases treated in hospitals 
beyond the forest zone have not caused the appearance of the disease in 
the staff of any hospital, although the virus has been found in the nose 
and throat and in the urine of encephalitis patients. In the laboratory 
there is no evidence of spontaneous spread from animal to animal. 

Infection of human beings appears to be definitely linked with blood 
sucking vectors, namely the pasture ticks, Ixodes persulcatus, which in 
the act of biting introduces the neurotropic filterable virus in its saliva. 
This statement is supported by the fact that most patients gave a definite 
history of having been bitten bv a tick eight to eighteen days prior to 
the onset of the disease. Practically all patients lived and \\'orked in 
forests in which ticks are abundant. The curve of the incidence of 
encephalitis parallels that of the tick population in nature. Ticks appear 
prior to the onset of the first cases each year. As the sexually mature 
forms of the pasture tick disappear, so also encephalitis vanishes from 
the population of the region. The geographical distribution of the tick 
population coincides with that of the cases of encephalitis. Forest areas, 
in which ticks are found rarely, do not show cases of this disease. There 
is evidence of immunity produced by frequent tick bites in areas in 
which infected ticks occur and in which the population has been long 
in residence. The resistance of such individuals can be accounted for by 
the presence in their blood of virus-neutralizing antibodies. Similar 
changes are found in the blood of the domestic and wild animals in the 
same areas, this being true of horses, cows, rodents and other wild 
animals. 

YoL. \'I. 750 



RUSSIAN SPRING-SUMMER ENCEPHALITIS 82(37) 

Considerable experimental evidence also incriminates the pasture tick 
as the vector of this disease. Ticks collected from areas, in which en- 
cephalitis is prevalent, quite regularly can be shown to contain the 
encephalitis virus. Intracerebral inoculation of mice with an emulsion 
of ground ticks causes the appearance of the picture of experimental 
encephalitis in these animals with a pathological picture similar to that 
of the human disease. The virus isolated from the brains of these mice 
is serologically identical with strains of virus isolated in a similar manner 
from human autopsy brain material. Negative results are secured from 
ticks collected in localities free of encephalitis. Several species of pasture 
ticks are readily infected when fed on infected mice. The virus persists 
for a long time in the body of the tick, and in the case of Ixodes persiil- 
catiis it is transmitted from generation to generation of ticks. Artificially 
infected ticks can transmit the disease also when they bite susceptible 
animals. The virus in the tick apparently is transmitted to subsequent 
generations in the ova and survive the winter period. Larvae hatched 
from ticks of infected areas are infected. Ixodes persidcatiis attacks men 
very actively and is the most common species of tick in the areas in 
which encephalitis is endemic. However other ticks such as Derma- 
centor siharinn and Haeitiopby salts conciiwa may act also as vectors. 

Another virus reservoir lies in the wild animals of infected areas. 
Encephalitis virus has been recovered from the bodies of a number of 
wild rodents in epidemic areas. The infection in animals may be latent 
or apparent. The disease therefore exists in nature independent of man. 



Etiology 

Characteristics of the Virus. — Like other viruses the causative agent 
of this disease is invisible on microscopic examination of infected 
material. No inclusion bodies have been found on study of tissue sec- 
tions. The virus can not be cultivated in the absence of living cells. It 
has been grown in tissue cultures of minced chick embryo in Tyrode 
solution with or without added rabbit serum. It is readily filtered 
through Berkefeld or Chamberlain candles and is well preserved in 
glycerin. 

White mice, monkeys, goats, sheep and many rodents are readily 
infected by the virus. The experimental disease in monkeys is very 
similar to that in man. Intracerebrally inoculated mice begin to show 
symptoms 4 to 10 days after injection. They manifest irritability, then 

Vol. VI. 750 



S2(38) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

somnolence, convulsions and muscle palsies. Death occurs in 6 to 24 
hours after symptoms appear. Mice are most susceptible by intracerebral 
inoculation, less so to intranasal, subcutaneous and intravenous admin- 
istration. 

This virus beloncjs to the genus Erro and has been given the specific 
name Erro silvestrir^^. 

According to the observations of Smorodintseff"^^ the strains of this 
virus so far isolated appear serologically identical. It differs from St. 
Louis encephalitis virus both in antigenic and immunogenic properties, 
there being no cross neutralization or immunity. It is more closely 
related to Japanese B encephalitis. Immune rabbit serum specific for 
Japanese B virus will partially neutralize Russian spring and summer 
encephalitis virus but not as completely as it neutralizes the Japanese B 
virus. Antiserum against spring-summer encephalitis will also show 
activity against Japanese B virus. Animals immunized against spring- 
summer virus are also immune against Japanese B virus, but those immune 
to B virus are not always fmmune to the Russian spring-summer virus. 

Casals"^® obtained somewhat different results. He found that Russian 
encephalitis and louping ill viruses showed a close relationship by com- 
plement fixation, neutralization and intraperitoneal cross-resistance tests. 
Intracerebral cross-resistance tests, on the other hand, failed to reveal 
any connection between them. Neither Russian encephalitis nor louping 
ill showed any relationship to Japanese B virus, St. Louis encephalitis or 
West Nile encephalitis. In agreement with Casals, Sabin^^^ found no 
serological relationship between Russian spring-summer encephalitis 
virus and a strain of Japanese B virus which he isolated on Okinawa in 
1945. There is, therefore, some contradiction in the serological relation- 
ship of these viruses in the reports so far available. 

Silber and Shubladze"^^ report certain differences between the tick- 
born encephalitis viruses isolated in A\'estern European Russia and strains 
isolated in Far Eastern Siberia. The Western strains they found to be 
serologically identical with louping ill virus in agreement with the 
findings of Casals"'^ The Far Eastern strains were serologically different 
and cause somewhat different symptoms when inoculated into sheep. 
The Western virus is transmitted by Ixodes ricinus, whereas the Far 
Eastern strain is transmitted by Ixodes per sid cams. 

According to Warren'^" encephalitis cases occurring in the autumn 
in Far Eastern Siberia are identical with Japanese B encephalitis. 

Vol. VI. 750 



RUSSIAN SPRING-SUMMER ENCEPHALITIS 82(39) 

According to the Russian observers virus neutralizing antibodies 
appear in the serum of infected' human beings rather slowly. Only 
about 10 per cent, show antibodies before the 15th day after the onset. 
By the 20th to the 30th day about 50 per cent, show the presence of 
virus neutralizing antibodies. After this nearly all cases show antibodies, 
and once they appear, they usually persist for many years. There ap- 
pears to be no parallelism between the level of serum antibodies and 
the gravity of the disease. 



Pathology 

In Russian spring-summer encephalitis severe inflammatory and de- 
generative changes are found not only in the brain and spinal cord but 
also in the sympathetic nervous system and the peripheral nerves. The 
pathological picture is that of an acute non-suppurative meningo- 
encephalo-polio-myelitis. The meninges show an acute serous men- 
ingitis. The brain is congested and shows numerous hemorrhages in 
the brain stem, the medulla and the horns of the spinal cord. The 
lesions are perhaps most marked in the medulla and the grey matter 
of the spinal cord, whereas in the cerebral cortex the changes are rela- 
tively slight. Microscopically the lesions show perivascular infiltrations 
of the blood vessels of the grey and white matter and the meninges and 
also diffuse focal infiltrations of the grey matter with inflammatory 
cells. These cellular infiltrations consist mostly of lymphocytes with a 
small number of polymorphonuclear leucocytes and glial cells. The 
ganglion cells of the medulla and cord show various degenerative 
changes from slight chromatolysis and loss of Nissl granulation to com- 
plete neuronophagia. Hemorrhages in the grey matter are seen quite 
frequently, varying greatly in size and number"^^. 



Clinical Course 

The incubation period is between 8 and 1 8 days. The onset is marked 
by a rise in temperature to 38° to 40° C. The patient complains of 
severe headache, pain in the muscles of the neck, vertigo and vomiting'^^ 

A\ eakness and paralysis of the muscles of the neck and shoulder 
girdle develop usually by the second or third day of the disease, "droop- 
ing neck" being a common symptom. In unfavorable cases the lesions 

Vol. VI. 750 



82(40) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEM 

ascend from the cervical cord to involve the basal ganglia of the brain 
with the appearance of grave bulbar symptoms. Disturbances in respira- 
tion, disturbed cardiac activity and difficulty in swallowing and phona- 
tion may be seen. Death often occurs suddenly between the 3rd and 8th 
day of the disease. 

The mortality is about 30 per cent., varying somewhat in different 
outbreaks. 

Convalescents frequently show persisting weakness, paralysis and 
atrophy of cervical muscles and the muscles of the shoulder girdle. The 
Parkinsonian syndrome which is a frequent sequel of lethargic enceph- 
alitis, apparently does not occur in this disease. 



Differential Diagnosis 

Russian spring-summer encephalitis differs from other types in its 
seasonal incidence which is highest in April, May and June. This should 
be contrasted with lethargic encephalitis which occurs chiefly in the 
winter and early spring. Also it differs from Japanese B encephalitis, 
St. Louis encephalitis, Eastern and Western equine encephalomyelitis 
and poliomyelitis, all of which occur in the late summer and early 
autumn. 

Spring-summer encephalitis is limited to tick-infested forest areas, 
whereas lethargic encephalitis is as common in the cities as in the coun- 
try. The late summer and autumn types such as Japanese type B and 
St. Louis encephalitis have involved urban areas, but in the case of the 
St. Louis epidemics the case incidence was higher in suburban and semi- 
rural portions of St. Louis County than in the city. Equine encephalo- 
myelitis has been found most commonly in rural areas. In none of these 
are heavily forested areas involved, nor has association with ticks been 
a prominent feature. Experimentally, it is true that St. Louis enceph- 
alitis can be conveyed to animals by tick bites, but this is not believed 
to be the common mode of transmission to mair^°. 

Spring and early-summer encephalitis appears to affect mostly young 
adults. This age incidence is somewhat similar to that of lethargic 
encephalitis but differs from St. Louis encephalitis and Japanese type 
B, which in most outbreaks have their. highest incidence in the older age 
groups. Poliomyelitis has its greatest incidence in young children. 

Vol. VI. 750 



RUSSIAN SPRING-SUMMER ENCEPHALITIS 82 (41 ) 

Russian spring-summer encephalitis frequently causes paralysis of 
the muscles of the neck and shoulder girdle, a picture rarely seen in 
other types of encephalitis. Parkinsonism is seen rarely in Russian 
encephalitis although a common sequel of lethargic encephalitis. Per- 
manent weakness and atrophy of the muscles of the shoulder girdle 
and neck is a common sequel of Russian encephalitis but rarely seen 
in other types. 

The differences in the serological reactions have been discussed 
already. 



Preventive Measures 

Since ticks play an all important role in the transmission of spring- 
summer encephalitis, measures to protect human beings from these in- 
sects are important in the control of this disease. Individuals working 
in forest areas should be examined regularly for the presence of ticks, 
and when found, these insects should be removed immediately and de- 
stroyed. It can be shown in experimental animals that the lens^th of the 
period during which the tick feeds on the animal is very important in 
the transmission of the disease. In mice blood sucking- for two to four 
hours will not transmit the disease, whereas feeding for two to four 
days will cause infection'^\ Examination of forest workers twice daily 
for ticks will greatly reduce the chance of infection. Protective clothing 
is of value, and the Russians have devised clothing of this type. 
Garments impregnated with insect repellants are also useful. Protec- 
tion of camp sites by burning grass and spraying with insect repellants 
has been shown to be effective. Finally efforts should be made to 
exterminate the wild rodents \\^hich serve as reservoirs of the infection. 

A protective vaccine has been prepared by Smorodintseff, Kagan 
and Levkovich"^'^ from emulsions of infected mouse brain in which the 
virus has been killed by incubation with 1/600 to 1/750 formaldehyde 
for 15 to 20 days at 2° to 5° C. Such a vaccine preserves its antigenic 
properties for about two months. This vaccine caused no unfavorable 
reactions. In a controlled study of its use it reduced the incidence of 
encephalitis to one-tenth that of the control group and reduced the 
mortality to one-third that of the controls. Casals and Olitsky""* also 
have prepared formalin inactivated Russian spring-summer encephalitis 
virus vaccines which produced lasting immunity in mice. 

Vol. \T 750 



82(42) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEM 

Treatment 

Russian investigators have used both human convalescent serum and 
immune horse serum in the experimental and clinical treatment of this 
infection. To be effective it must be administered on the first or second 
dav after the onset. It may be administered both intramuscularly and 
intraspinallv. Oxygen inhalation apparently is of some value in treat- 
ment. The Russians also use urotropin and believe it to be of some value. 
They admit that serum treatment does not guarantee the patient against 
serious complications or even death and that further study of a satis- 
factory method of treatment is needed"^". 



Vol. VJ. 750 



EPIDEMIC SUMMER ENCEPHALITIS 82(43) 

GROUP III 

Types of Encephalitis With Time of Onset Chiefly 

But Not Exclusively in the Late SumxMer 

And Autumn 

EPIDEMIC SUMMER ENCEPHALITIS, ST. LOUIS TYPE 

Definition. — An acute infectious disease caused by a filterable virus, 
characterized by non-purulent inflammation of the brain with conges- 
tion and perivascular infiltration of lymphocytic and mononuclear cells. 
The clinical picture includes a high but irregular fever, accompanied by 
severe headache and by signs of meningeal irritation, usually somnolence 
and at times, delirium and coma. Non-fatal cases terminate after a 
course of one to three weeks. Serious chronic nervous residuals are rare. 

Historical Account 

The first definitely recognized outbreak of this disease occurred in 
Paris, Illinois, between July and September 1932. While the total num- 
ber of cases was small, the incidence per 100,000 population and the 
mortality were both higher than in any of the subsequent epidemics. 
One year later a second epidemic occurred in the vicinity of St. Louis. 
Missouri. This epidemic, while most intense in St. Louis City and 
County, spread across the Mississippi river to involve neighboring com- 
munities in Illinois and also was known to have appeared in Columbia, 
Kansas City and St. Joseph, Missouri and in Louisville, Kentucky". An 
examination of the mortality statistics of the United States census for 
this year shows that deaths from encephalitis in this year exhibit a curious 
preponderance of summer over winter deaths in a large number of states. 

A white, male, 17 years of age, whose illness began July 5, 1933 
with fever, chills and headache, was treated at Firmin Desloge Hospital 
in St. Louis from the seventeenth to the twenty-first of July. The cell 
count of the spinal fluid was elevated, and the neurological findings were 
considered by Dr. L. B. Alford to be suggestive of encephalitis. Sub- 
sequently virus neutralization tests showed that this case probably was 
a case of true St. Louis encephalitis. This individual was a resident of 

Vol. VI. 750 



82(44) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

the west central part of the city of St. Louis but near the border of the 
city and county. The greater number of the earher cases of the epi- 
demic occurred in St. Louis County and were treated and diagnosed at 
St. Louis County Hospital. The epidemic nature of the outbreak was 
recognized by the staff of the Health Division of the City of St. Louis 
on August 8th. Reported cases reached their maximum in St. Louis 
County the week of September 2nd and in the city the week of Sep- 
tember 16. The disease had practically disappeared in the county by 
the week of October 2 i and in the city the week of November 1 1 . The 
disease, therefore, appeared in epidemic proportions first in the county 
and reached its maximum and subsided at an earlier date in the county 
than in the city. When studied regarding the day of onset of illness, 
more city cases had their date of onset on August 27 than on any other 
day'^ The seasonal occurrence noted in the vicinity of St. Louis was 
very similar to that seen in all areas in which the presence of this disease 
was recognized. 

After the epidemic of 1933 the disease apparently disappeared in the 
vicinity of St. Louis except for a few doubtful sporadic cases until the 
summer of 1937, when a second outbreak occurred of about two-thirds 
the proportions of the first epidemic*-. The seasonal incidence and 
spread of this outbreak was quite similar to that of the epidemic of 1933. 
Since this time St. Louis encephalitis has been recognized in various 
parts of the United States"^^' '"^' 



138. 139. 242, 243 



GeoGRAPH ICAL DiS tRIBU riON 

The local geographical distribution of cases in both outbreaks in 
relation to population is extremely interesting. The case incidence per 
100,000 population in 1933 was 69 in the city of St. Louis, 212 in St. 
Louis County. In the city the oldest and most densely populated areas 
had a lower incidence rate than those newer sections of tlic city, which 
bordered on St. Louis County. A more detailed analysis of case distri- 
bution has been made by Casey and Broun'^l In this study the area of 
the city and county was di\idcd off into circular zones, one mile in 
diameter. The case incidence of encephalitis in each circular area was 
compared with the population density of the same area. In this way it 
was possible to determine exactly what areas showed a case incidence 
greater than would be expected from the population density. This study 

Vol. VI. 750 



EPIDEMIC SUiMMER ENCEPHALITIS 82(45) 

showed that the areas, where encephalitis was prevalent out of propor- 
tion to that which would be expected from the population density, were 
all situated "within one mile and all except one within one-half mile of 
the small streams in St. Louis and St. Louis County. The streams all or 
nearly all carried sewage." The survey revealed a fairly close correlation 
between the occurrence of epidemic encephalitis foci and lack of outdoor 
sanitation in an area as judged by the presence of weeds, open sewas^e, 
ponds, streams, garbage and tincan dumps. Ninety-five per cent, of the 
inhabited wood, open sewage, stream and pond areas of St. Louis showed 
a significant (P-o.oi) or probably significant (0-0.005-0.01) preponder- 
ance of encephalitis, and 87 per cent, of all cases occurred within a mile 
of such an area. Every district in the St. Louis area, which was without 
weeds, open sewage, and ponds, and which was separated a mile or 
more from such an area, was not only without heavy concentrations 
of encephalitic cases but actually showed a statistically significant 
scarcity of encephalitis. About 4 per cent, of the population of St. 
Louis lived under these fortunate conditions. The prevalence of enceph- 
alitis in sewage, stream pond and weed areas could not be explained on 
the presence of more old people in these areas as a control study was 
made regarding this point. Nor could poverty and poor indoor sani- 
tation explain it, since the areas of greatest poverty and most unsatis- 
factory indoor sanitation had the least encephalitis in the St. Louis area. 
On the other hand, foci did occur in districts, where the inhabitants 
were wealthy and above average in wealth, where these areas were 
within one-half mile of streams and ponds and open sewers. The dis- 
ease did not tend to predominate in the more congested areas but 
actually predominated in the most sparsely settled areas of the city 
and county. 

Regarding the types of dwellings in which cases of encephalitis 
occurred, a survey of 1 3 3 cases showed that 1 1 1 lived in single houses, 
10 in flats and 12 in apartments. This again indicates that most cases 
were not from the most crowded districts. About 1 5 per cent, of cases 
reported known contact with other cases of encephalitis. In less than 
10 per cent, of cases more than one case occurred in the same family. 
In many households the least mobile member and the one least in con- 
tact with the outside world, e.g., an individual bed-ridden from chronic 
illness, was the one stricken^'. 

All of these features differ from diseases known to be spread by con- 
tact. They are all identical with facts known about diseases which might 

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82(46) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEM 

be spread bv mosquitoes or orher insect vectors. The present status of 
knowledge regarding the possibility of mosquito transmission will be 
discussed presently. 



Climactic Conditions 

Both the 1933 and 19^7 outbreaks of encephalitis occurred during a 
period of drought and intense heat. During June, July and August of 
1933, according to official weather bureau records, the rainfall in St. 
Louis and St. Louis County was the lowest in its history up to that date. 
The drainage and sewage disposal was favorable to the breeding of un- 
usually large numbers of mosquitoes in areas commonly infested. With 
the dry season the flow in these open ditches was very small and prac- 
tically consisted of sewage only and odors that emanated from these 
places were quite offensive^". In 1937 while the rainfall in June was 
somewhat more abundant x\ugust was both hot and dr\^ Mosquitoes 
were again present in great numbers. 

It is of interest to note that the epidemics of Japanese summer en- 
cephalitis also occur during periods of drought and intense heat. 

However, before too much stress be laid on climatic conditions, the 
fact must be recorded also that during the hottest and driest of all sum- 
mers in the St. Louis area, that of 1936, the disease did not reappear in an 
incidence sufficient for recognition. In this summer it is true that the 
small streams and ponds w^re mostly completely dried up, and the 
summer was not marked by the prevalence of great numbers of mos- 
quitoes and other insects. 

Age And Sex Incidence 

In both epidemics the disease occurred in all age groups but showed 
a definitely higher incidence in the higher age groups more so than in 
almost any other known infection except Japanese encephalitis'" (see 
Table III). The mortality also is higher with advancing years. 

The sex incidence was practically identical with the sex distribution 
of the population; 50.9 per cent, males, 49.1 per cent, females. The 
colored race, numbering about 10 per cent, of the population, had 
slightly less than 10 per cent, of all cases'^ 

Vol. VI. 750 



EPIDEMIC SUMMER ENCEPHALITIS 
Mortality 



«2(47) 



The mortality of reported cases of St. Louis encephalitis durincr the 
epidemic of 1933 was 18.7 per cent. The recurrence of 1937 showed in 
the city of St. Louis a death rate of 24.8 per cent. In both outbreaks the 
increased mortality with advancing years was seen clearly. In addition 
the mortality of cases, which had definite hypertensive vascular disease 
during the attack of encephalitis, was quite high in all age groups. In a 
series of 129 cases, treated at Firmin Desloge Hospital in 1933, 32 cases 



Age 
Period 



40-49 



50 and 
above 



TABLE III 

Age Incidence of Neurotropic Virus Diseases 

Eastern Western 
Lyiiiphocytic Equine Equine 

Encephalitis St. Louis Chorio- Evcepbalo- Encepbalo- Polio- 

Letbargica Encephalitis meningitis inyelitis myelitis myelitis 



0- 9 


75 cases 
(16.2%) 


28 cases 
(84%) 


8 cases 
(74%) 


5 cases 
(65.2%) 


8 cases 
(22.2%) 


(81%) 


10-19 


108 cases 
(234%) 


24 cases 

(7-2%) 


10 cases 
(9-3%) 


1 cases 
(25.0%) 




(12%) 


20-29 


1 07 cases 
(23.2%) 


33 cases 
(9-9%) 


30 cases 

(27.7%) 






(4%) 


30-39 


66 cases 
(14-3%) 


30 cases 
(9-0%) 


31 cases 
(28.7%) 




2 9 cases 
(694%) 





53 cases 
(114%) 



41 cases 

(12.3%) 



1 8 cases 
(16.7%) 



I case 
(12.5%) 



53 cases 
(114%) 



178 cases 
(53-2%) 



1 1 cases 
(10.2%) 



3 cases 
(84%) 



(3%) 



had hypertension. In this hypertensive group the mortality was 3 i per 
cent., whereas the entire group had a mortality of only 12.3 per cent.*^. 
Very young children show a higher mortality than those in the other 
lower decades. 



Etiology and Epidemiology 



The majority of the studies of the etiology of St. Louis encephalitis 
have failed to reveal evidence of the presence of bacteria in the brain 
Vol. VI. 750 



82(48) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

tissues except In cases with secondary infections^'. Rosenow^* reported 
isolation of streptococci in cases which he studied. For a full discussion 
of the evidences regarding bacteria as a causativ^e factor the report of the 
St. Louis outbreak of encephalitis, published by the Public Health 
Service, should be consulted^'. 

The disease was transmitted successfully to macacus rhesus monkeys 
by Muckenfuss, Armstrong and McCordock**' by intracerebral inocu- 
lation with brain material secured at autopsy from human cases of en- 
cephalitis. Many monkeys were, however, resistant to the infection, and 
it was found difficult to insure perpetuation of the infection in this 
animal. 

Webster and Fite^", using brain material preserved in glycerin, trans- 
mitted the disease to white mice and in this animal secured uniformally 
fatal results with definite doses of brain material. They established the 
fact that the agent was filterable and hence presumably a virus. They 
also sho\\'cd that the convalescent serum of cases of St. Louis encephalitis 
would neutralize this virus and protect inoculated animals from otherwise 
fatal doses. This test has been extremely valuable in subsequent studies 
of this infection. 

The virus, which they isolated, is now generally accepted as the 
causative agent of St. Louis encephalitis. It has been classified as belong- 
ing to the viruses of the genus Erro and has been designated Erro 
selesti/s'-^^. 

Later Muckenfuss, Annstrong and McCordock transmitted the virus 
from previously infected monkeys to mice''. Broun, Muether and 
Collier"*' established two strains of the virus in mice from human brain 
material, which had been preserved nearly three months in glycerin. 
Greutter, Broun and Muether isolated the virus from human brain ma- 
terial in the 1937 outbreak in St. Louis proving the identity of the infec- 
tion in this year with that of 1933*". 

AA'ebster and Fite**'* have reported that serum of convalescents from 
Japanese encephalitis does not neutralize tiic St. Louis virus, thus estab- 
lishing a serological difference between these clinically highly similar 
infections. Sera of patients convalescent from the von Kconomo type of 
lethargic encephalitis fail to show neutralizing antibodies against the St. 
Louis virus, indicating a serological difference between these two 
diseases^'. 

Mice can be incx;ulated successfully with the virus by intranasal as 
well as intracranial inoculation. Subcutaneous and intraperitoneal inocu- 

VoL. VI. 750 



EPIDEMIC SUiMiMER ENCEPHALITIS 82(49) 

lations fail to produce encepahlitis, unless the brain has been injured pre- 
viously. When the virus is given subcutaneously, it acts as a vaccine 
protecting mice against subsequent intracranial inoculation for a period 
beginning 4 to 7 days after the injection and usually lasting about 8 
weeks^°. A curious fact, noted by Webster, is that during the period of 
cerebral immunity, following subcutaneous vaccination, the serum of the 
mice contains no virus-neutralizing antibodies. When the cerebral im- 
munity is lost, virus-neutralizing antibodies appear in the serum^\ 

The ease with which white mice can be infected with the virus of 
St. Louis encephalitis naturally led to interest in wild mice as a possible 
source of infection. At least three varieties of wild mice have now been 
shown to be highly susceptible to infection by this virus. Harford, 
Sulkin and Bronfenbrenner"^ showed that the house mouse, Alns imis- 
culus, can be infected. Greutter, Fulton, Aluether, Hanss and Broun^^ 
have demonstrated that the field mouse, Reitbrodovtouiys inegalotis, and 
the meadow mouse, Microtus ocbrogaster, are susceptible also. All three 
of these types of mice are common in the vicinity of St. Louis. Mice 
trapped in the homes of encephalitic patients to the present time have 
not been found to be carriers of the virus. \A'hile mice, therefore, are a 
potential source of infection, they have not been shown to be involved 
in the causation of the epidemics so far studied. 

The successful transmission of St. Louis encephalitis to the hamster 
was reported by Broun, Muether, Mezera and LeGier"^ in 1941. This 
provided investigators of this disease with a readily available susceptible 
laboratory animal of larger size than the mouse for serological studies"^ 

The question of a gastrointestinal portal of entry has been raised 
by the work of Harford, Sulkin and Bronfenbrenner^-. Ordinarily it is 
rather difficult to infect animals by this route, and there is question 
whether contamination of the nasal mucosa does not occur during inges- 
tion of the infected material. Mezera"^ has shown that administration of 
St. Louis encephalitis virus by mouth to hamsters is followed by the 
appearance of virus neutralizing antibodies in the blood, although no 
obvious illness is produced. 

The possibility of mosquito transmission of the virus of St. Louis 
encephalitis w-as studied during and following the epidemic of 1933. 
Mosquitoes were allowed to bite volunteer convicts in the state peniten- 
tiary after biting cases of encephalitis. These experiments gave uni- 
formly negative results". 

Later \\'ebster. Clow and Baue^'^ working with anopheles mosqui- 
toes, showed that the virus is taken into the body of the mosquito from 

Vol. VI. 750 



82 (5o) ENCEPHALITIS AND OTHER X'IRUS INFECTIONS 
OF THE CENTRAL NER\'OUS SVSTEAI 

infected mice and survives for a period as long as 28 days, even increasing 
in amount during this time. However, allowing the infected mosquito 
to bite another mouse did not give rise to disease in that animal. As 
mentioned above, subcutaneous injections of virus usually are ineffective 
in securinc^ infection of the brain in animals inoculated by this route. 

Fulton, Greutter, Aluether, Hanss and Broun"^ reported similar 
results in experiments in which Cjilex pipieiis, secured from the St. Louis 
area, were allowed to bite mice heavily infected Vvith the virus of St. 
Louis encephalitis. The virus could be demonstrated in the body of this 
mosquito after biting an infected animal, but subsequently, when these 
mosquitoes bit another animal, in no case did these develop encephalitis. 
Adult mice were used in these experiments. Other investigators subse- 
quently showed that use of newborn mice greatly facilitated transmis- 
sion experiments of this type. 

Blattner and Hevs'-^" have shown that St. Louis encephalitis may be 
transmitted to young mice by the bite of ticks. The location and distri- 
bution of cases as well as the individual histories obtained from patients 
during the St. Louis epidemics of 1933 and 1937 do not suggest a tick- 
borne disease. These experiments, however, indicate the possibility of 
this mode of spread in certain cases. They have isolated the virus of St. 
Louis encephalitis from the blood of a human case"^\ 

In 1934 Broun, Aluether and Collier''' reported that a high percentage 
of the cases of St. Louis encephalitis, observed in the epidemic of 1933, 
had had close contact with chickens. In 1941 Hammon, Gray, Evans 
and Izumi"'" reported the presence of virus neutralizing antibodies against 
St. Louis encephalitis virus in the sera of \\ild and domestic mammals 
and birds studied in the Yakima A^'allev of AA'ashington where an epi- 
demic of this disease occurred. Of the sera of 77 domestic mammals 
studied 37 per cent, protected against the St. Louis virus in contrast to 
9 per cent, of 65 wild animals. A lore striking still were the findings in 
the sera of chickens and other domestic birds ^here 50 per cent, showed 
protection against St. Louis virus compared to 15 per cent, of 87 wild 
birds. These findings were significant in that they indicated domestic 
fowls and animals could serve as a potential reser\'oir for the St. Louis 
virus. They found that the distribution of cases in the Yakima A'^allev 
supported this supposition, namely that domestic fowl may have served 
as the source of the infection. Further studies by Hammon and Reeves"^' 
disclosed the presence of St. Louis encephalitis virus in mosquitoes of the 
species Culex tarsaUs captured in the Yakima A'^alley. While guinea pigs, 

\^oL. AT 750 



EPIDEMIC SUMMER ENCEPHALITIS 82(51) 

cats and horses showed no viremia after inoculation with St. Louis 
enccphahtis virus, birds, particularly chickens, ducks and doves devel- 
oped viremia. Subcutaneous inoculation of 0.2 c.c. of the dilution of 
virus which killed 50 per cent, of mice when 0.03 c.c. was inoculated 
intracercbrally produced viremia in 5 of 6 chickens. Furthermore, the 
virus multiplied in the chickens to such an extent that tenfold and occa- 
sionally hundredfold dilutions were infectious for mice. These experi- 
ments showed that the moscjuito might acquire the virus by biting 
infected chickens and then transmit the virus to other chickens, ducks 
and doves. The infected fowl show no obvious illness"'^\ Subsequent 
studies have shown that many species of mosquitoes may transmit en- 
cephalitis virus. These are Ciilex tarsiilis, Ciilex pipiens, Culex corovator, 
Anopheles lateralis, Anopheles nigroniaculis, Culex mcidens and Cnlex 
iiwrjhtta. Survival of the virus but no transmission occurred in Culex 
qmuquej asciatus , Culex stiguiatosoina, Fsoraphora ciliata and Anopheles 
niaculopennis Freeborni. These investigations indicate that fowl may 
serve as a reservoir of St. Louis virus in nature and that mosquitoes may 
serve as the vector by which the disease is transmitted from fowl to 
man-^^ 

Another link in the chain of the epidemiology of St. Louis encepha- 
litis was furnished by the studies of Smith, Blattner and Heys"^'' in 1944. 
They reported the isolation of St. Louis encephalitis virus from chicken 
mites, Derinanyssus gallinae, found on chickens in the vicinity of St. 
Louis. The sera of these chickens showed the presence of antibodies 
against St. Louis encephalitis. The mites not only were shown to carr)' 
the virus but to pass it from generation to generation in the process of 
breediner. AA'hile these mites are not believed to bite man, it is believed 
that they maintain the infection in chickens of an endemic area, and 
when circumstances are favorable, an epidemic may arise from such a 
focus. The present conception would make the actual transfer of infec- 
tion from fowl to man take place by mosquito transmission. 

The pathology of this disease has been described carefully by Mc- 
Cordack and Collier". The essential pathological process is an acute, 
nonpurulent inflammation of the central nervous system characterized 
by intense vascular congestion with petechial hemorrhages, cellular infil- 
tration of both nervous tissue and meninges with various types of mono- 
nuclear cells and evidences of toxic degeneration in the nerve cells. 

On opening the meninges it was noted that the amount of cerebro- 
spinal fluid WAS increased in most cases, where it had not been drained 
recently by lumbar puncture. L.very brain examined showed grossly 
Vol. VI. 750 



82(52) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEM 

obv^ious congestion of meningeal and intracerebral vessels often with 
minute hemorrhages. The cut surface often showed a Hght, salmon-pink 
color due to intense capillary congestion. This was sometimes diffuse, 
more often blotchy, in distribution. Increased softness of the brain tissue, 
due to edema, was encountered often. 



Pathology 

The chief changes found in the nervous system on microscopic ex- 
amination were vascular congestion and hemorrhages, cellular infiltra- 
tions and nerve cell degeneration. The vascular congestion was wide- 
spread and involved vessels of all sizes down to capillaries. Cellular 
infiltrations of three types were noted: ( i ) perivascular cuffs around 
the blood vessels consisting chiefly of lymphocytes but with occasional 
mononuclear and a few polymorphonuclear cells; (2) scattered foci in 
the brain tissue, not in connection with blood vessels, of mononuclear 
cells some being lymphocytes and others probably of glial origin. De- 
generated nerve cells were seen sometimes in these foci; (3) diffuse 
cellular infiltrations of the brain tissue, sometimes slight and sometimes 
very marked. 

The meninges, while never showing a frank exudate, showed micro- 
scopic infiltrations of mononuclear cells in some three-fourths of all 
cases examined. In one-fourth of the cases these infiltrations were well 
marked. These infiltrating cells were chiefly lymphocytes and plasma 
cells with, occasionally, large mononuclear phagocytes and rarely, a few 
polymorphonuclear leucocytes. Pathological changes in nerve cells of 
varying degree and distribution were found in practically all cases. 
Perinuclear chromatolysis, eccentric nucleus, swollen nucleolus and ex- 
cess of pigment were seen commonly. Shrinkage of nerve cell body 
with pycnotic nuclei and darkly staining or practically liquefied cyto- 
plasm was seen in cases showing extensive cellular infiltrations. 

Amyloid bodies, sometimes described as occurring in young indi- 
viduals with lethargic encephalitis, were seen chiefly in aged individ- 
uals with the St. Louis type. Perixascular patches of demyelination, 
considered to be quite characteristic of post-vaccinal and post-measles 
encephalitis, were never found. 

Examination of the proximal ends of the cranial nerves showed only 
slight ciianges in these, chiefly in the optic and trigeminal nerves. 

\'oi.. \'I. 750 



EPIDEMIC SUAIAIER ENX:EPHALITIS 82(53) 

The congestion and minute hemorrhages occurred diffusely through- 
out the brain and cord. Cclkilar infiltrations in sonic cases with in- 
tense reaction occurred in all parts of the brain; in others they were 
limited to the pons, more often to pons, mid-brain, basal nuclei and 
white matter of the cerebrum. Nerve cell degeneration, while often 
seen in the cortex, was more frequent in the pons, basal nuclei and 
medulla. 

In a few instances focal bacterial lesions were found in the brain. 
However, these cases had other evidences of sepsis, and the bacterial 
lesions \^'ere considered m.erely evidences of a septic complication such 
as in one instance pneumonia and in another pyelonephritis. 

Since most of the indixiduals coming to autopsy were of advanced 
years, the evidences of arteriosclerotic changes in brain, heart, kidney, 
etc. were often definite and striking. Fully 6^ per cent, of cases showed 
arteriosclerotic thickening of the arterioles. Arteriosclerotic nephro- 
sclerosis was found in perhaps one-fourth of all cases, and myocardial 
lesions due to the same process in a somewhat smaller percentai^e of cases. 

Bronchopneumonia was the most frequent terminal complication. 
Usually it was of the purulent lobular type. However, in some cases the 
pneumonic process resembled closely acute hemorrhac^ic influenzal 
pneumonia with destruction of bronchial epithelium, thickening and 
hyperemia of bronchial walls and a hemorrhagic alveolar exudate with 
small areas of necrosis of lung tissue. 

About one-third of all cases showed an acute change in the kidneys, 
apparently related to the disease itself. This consisted of swelling and 
intense conei^estion of blood vessels with petechial hemorrhages in the 
pelvic mucosa. Intranuclear inclusions were observed in the epithelial 
cells of the convoluted tubules and of Henle's loops in a number of 
instances^^ 

The differences in the pathology of St. Louis Encephalitis as con- 
trasted with the von I'xonomo type of lethargic encephalitis are as 
follows: 

1. The meninc^es show more intense infiltration with mononuclear 
cells than is usually found in the lethargic type. 

2. Inflammatory foci are more ^\'idespread throughout the brain, 
often occurring in great numbers in the cerebral cortex, and are not 
restricted to the mid-brain and basal ganglia. 

3. Des^enerati\e changes in the nerve cells are more frequent, and 
neuronophagia is more marked, 

Vol, y\. 750 



82(54) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\^OUS SYSTEM 

4. The nerve cells in the nuclei of the craniid nerves, especinllv the 
third, rarely shows degenenitive changes. 

5. There is more extensive involvement of the spinal cord. 
These differences are best noted in the early cases of the epidemic 

with intense inflammatory reaction. Later cases individually might be 
difficult to differentiate on a pathological basis. 



iNCUBAtlOX PfRIOD 

At least eight individuals are known to have developed encephalitis 
from 4 to 14 days after leaving the St. Louis area and showing an in- 
cubation of at least 4 and as high as 14 days. Six cases developed enceph- 
alitis between 9 and 2 i days after entering the area involved by the 
epidemic, showing incubation periods no longer than 9 to 2 i days''. 



Clixicai. Course 

The disease most often is of sudden onset. However, in a con- 
siderable percentage of cases malaise, headache, dizziness and myalgia 
preceded the acute onset by a period of several days. Symptoms of 
coryza were described during this period in only some 14 per cent, of 
all cases. Actual sore throat was equally rare as an initial symptom. 
Occasionally gastrointestinal symptoms such as nausea and diarrhea 
preceded the onset of encephalitic symptoms. 

Sometimes chills, but more often chilly feelings, occurred at the 
onset in about one-fourth of all cases. The fever, as a rule, rose rapidly 
after its onset to attain levels within 48 hours around io3°F. in the 
average case. Its subsequent course was quite irregular. The duration 
of febrile period varied between 3 and 37 days with an average duration 
of 12 days after the onset. Ljght cases out of 128 had a fever lasting 
longer than 2 i days. The fever curve was quite irregular showing in 
some instances two or even three waves of fever of se\'eral days dura- 
tion dropping almost to normal between. The final decline usually 
was by lysis rather than by crisis. Extreme hyperpyrexia was seen 
often in severe fatal cases. The isolation period of three weeks recjuired 
by the health authorities usually permitted fairly complete recovery 
before discharge from the hospital. 

Vol.. \T 750 



EPIDEMIC SUMMER ENCEPHALITIS 82(55) 

Therefore, in contrast to the winter von Economo type of enceph- 
ahtis, we are deahng here with a definite febrile illness. Furthermore, 
the nervous symptoms, presently to be described, are usually more 
severe in those cases with the highest temperature, and cases with low- 
fever usually have few^ nervous manifestations. With the return of 
temperature to normal levels most cases quickly recovered from the 
nervous symptoms associated wdth the disease. 

Headache was one of the most common symptoms being nearly 
universally present. Often located in the front and top of the head, it 
was described as dull, constant, often stupefying pain^'. Accompanying 
the headache general aching of muscles was noted frequently, some- 
times most markedly in the muscles of the back and neck. 

Definite somnolence was present in approximately two-thirds of 
all cases. It deepened to coma in about one-fourth of all cases. Mental 
confusion and irrationality occurred in about 40 per cent, of cases, often 
w'ith active delirium. 

In contrast to the von Economo type of lethargic encephalitis, 
cranial nerve palsies were rare. Diplopia occurred in less than 10 per 
cent, of cases and, as a rule, was transitory. Unequal or irregular pupils 
and sluggish or absent light reflexes were observed occasionally. 
Nystagmus was present in about 10 per cent, of cases. Ptosis was com- 
paratively rare. A few cases noted difficulty in sw^allowing. Motor 
aphasia w-as noted occasionally. 

Neck rigidity usually was present during the acute stages of the 
disease. A positive Kernig's sign was noted in about one-fourth of all 
cases. There was observed in nearly one-third of all cases a s;-eneralized 
spasticity of the muscles. This sometimes w^as merely a feeling;- of re- 
sistance to passive movement, but in other instances a marked spasticity 
occurred. Muscular tremors of various distribution and severity also 
were seen often, particularly tongue tremor, which was quite common. 

Nausea and vomiting were of frequent occurrence but seldom per- 
sisted very long. These appeared at times to be associated with increased 
spinal fiuid pressure. Abdominal and cremasteric refiexes in many cases 
were diminished or absent. Tendon reflexes varied in activity, sometimes 
being exaggerated, sometimes diminished, sometimes unequal. Patho- 
logical toe signs (Babinski's sign) usually w^re present at some time 
during the disease but varied in type and location from day to day and 
even from hour to hour. Ankle clonus was present rarely. 

Evidences of involvement of organs other than the nervous sv^stem 
occasionally appear. The most important w-as the development of 

Vol. VI. 750 



82(56) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

pneumonia. This occurred as a terminal event in a number of fatal cases. 
A relatively slow pulse in relation to the height of the fever was noted 
sometimes in the early part of the febrile period, often to be followed 
by rather marked tachycardia, which at times persisted into con- 
valescence"^ 

Pre-existing pathological conditions, particularly arteriosclerotic and 
hypertensive vascular disease, were present often to complicate the clini- 
cal picture. In a series of 130 cases, treated at Firmin Desloge HospitaP'^ 
it was noted that cases with pre-existing hypertension showed a dis- 
tinctly high mortality from the encephalitis infection. Several deaths, 
which occurred from i month to 4 years after the acute illness, showed 
evidence of advanced cerebral vascular disease. 



Laborajory Findings 

Urinary findings except in those cases with pre-existing complica- 
tions usually were normal. Moderate albuminuria together with a few 
red corpuscles and leucocytes were seen occasionally. In several in- 
stances cystitis and pyelitis with accompanying pyuria developed as 
complications. 

The leucocyte count varied in different cases between leucopenia as 
low as 5,000 to a leucocytosis as high as 20,000. On the average a slight 
polymorphonuclear leucocytosis occurred. The Schilling differential 
count showed in most instances a moderate shift to the left. However, 
in few infections of ecjual febrile reaction is a definite shift to the left 
in the differential count so often missing. There was no tendency for 
anemia to develop either during the acute phase or during convalescence. 

The blood non-protein nitrogen was normal except in cases of 
marked dehydration or with preceding renal complications. Blood 
sugar usually was normal but tended to show slightly higher than average 
figures. 

The spinal fiuid nearly always was clear, rarely slightly turbid or 
bloody. The pressure often was somewhat increased. Globulin fre- 
(jucntly was increased to a moderate extent. Spinal fluid sugar in most 
instances was normal, occasionally slightly elevated. There seemed no 
particular tendency to false positive Wassermann or Kahn tests either 
in spinal fluid or blood. 

1 lie colloidal gold reaction in the spinal fluid showed a moderate 

Vol. VI. 750 



EPIDEMIC SUMMER ENCEPHALITIS 82(57) 

change suggesting the tabetic type of curve in most instances. During 
the febrile stage the average curve found was as follows 11 1232 1000. 
During the early stages of convalescence after subsidence of the fever 
the average colloidal gold curve was 11 1222 1000. Colloidal sj-old re- 
actions performed several months and even several years after the acute 
phase, while usually found normal, in some instances showed a persisting 
alteration, one of the most persistent of the clinical laboratory fingings. 
Thus case #33-11081 seen in St. Louis during the acute phase of 
the disease in September of 1933 more than 14 months later had a 
colloidal gold curve showing 122332 1 11. Several other cases had lesser 
degrees of reactions after an equally long period. 



The Virus Neutral izatioji Test 

The fact that the convalescent serum of cases of St. Louis encephalitis 
contained neutralizing antibodies against the virus which causes the dis- 
ease was shown by Webster and Fite^^^ The value of this test in the differ- 
ential diagnosis of the disease was demonstrated by Broun and Ruskin*^. 
It is of value in eliminating other virus infections of the nervous system 
as well as eliminating confusing conditions due to other causative agents. 

The technique of this test is as follows"^ A serum specimen is col- 
lected close to the time of onset as well as a convalescent serum secured 
at least 2 weeks, and preferably longer, after the onset of the disease. 
In the test each serum is mixed with equal parts of a suspension of an 
emulsion in Locke's solution of the brain of a mouse dying of St. Louis 
encephalitis. Various dilutions of mouse brain, usually 1/10,000 to 
1/1,000,000, ordinarily are used. The serum-virus mixtures then are 
incubated for 2 hours at 37° C. White mice then are inoculated intra- 
cerebrally with the serum-virus mixture in the quantity of 0.025 c.c, 3 
to 6 mice being used for each dilution. Controls of equal quantities of 
virus suspensions and normal human serum and a known positive pro- 
tecting serum and virus mixture should be run simultaneously. 

Those serum-virus mixtures, which permit at least 50 per cent, sur- 
vival of the inoculated mice, while controls in the same dilution of virus 
and normal serum fail to give this protection, are considered to contain 
neutralizing antibodies. 

In a considerable percentage of cases both in the St. Louis epidemic 
of 1933 and that of 1937 negative virus-neutralization tests were found 
in cases which clinically appeared to be typical cases of St. Louis 

\^OL. VI. 750 



82(58) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

encephalitis. Thus Muckenf iiss and associates^"" found 2 2 per cent, with 
negative tests in cases from the 1933 epidemic. In our experience with 
cases from the 1933 epidemic and also from the 1937 outbreak we found 
about 20 per cent, of the convalescent sera gave negative results. These 
cases must either fail to develop neutralizing antibodies, or thev may 
represent cases of other neurotropic virus diseases with similar clinical 
manifestations. There is already evidence in the literature that lymph- 
ocytic choriomeningitis"" and western equine encephalomyelitis^" "" 
may occur simultaneously with cases of St. Louis encephalitis. It is also 
noteworthy that the 1937 outbreak of encephalitis in St. Louis was 
accompanied by an increased incidence of poliomyelitis. Some obscure 
cases occurring during encephalitis epidemics may represent cerebral 
forms of poliomyelitis. The neutralization tests with these and other 
neurotropic viruses, which now are available, will have to be carried 
out in each case to determine the true diagnosis. 

The use of the complement fixation test in the diagnosis of encephali- 
tis and rabies was described by Casals and Palacios"" in 1941. This 
test has been used with successful results in the clinical diagnosis and 
epidemiological study of Japanese encephalitis by Sabin^". It is ap- 
plicable to the study of St. Louis encephalitis. In a group of 50 appar- 
ently normal medical students, residents of the state of Aiissouri, whose 
sera were collected in 1949 and tested by the complement fixation reac- 
tion as^ainst St. Louis encephalitis virus in the author's laboratory, four 
showed a positive reaction, although in low titre ( % to 1/16). This 
suggests continued exposure to this virus in the St. Louis area. 



Residuals of St. Louis Encephalitis 

One of the most striking differences between St. Louis Encephalitis 
and the von Economo type of winter encephalitis lies in the paucity of 
serious nervous residuals in the case of St. Louis encephalitis. The find- 
ings of a recheck of cases, made one year after the epidemic of 1933, 
has been described by Bredeck, Broun, Hempelmann, AlcFadden and 
Spector'"". Fifteen years of subsequent experience with the 1933 cases 
has not materially altered the picture as reported after one year. Parkin- 
sonism, so common as a chronic residual of winter encephalitis, is con- 
spicuous by its absence. The great majority of cases have been able to 
resume their previous occupations. Fully two-thirds report their health 

Vol. M. 750 



EPIDEiMIC SUMMER ENCEPHALITIS 82(59) 

ro be as good or better than before the attack of encephahtis. The most 
common residual noted is a tendency to frequent headaches. Nervous- 
ness in the sense of excitabiHty and irritabiUty is quite frequent. In only 
a few instances do these reach proportions which seriously disturb 
family relationships. Forgetfulness is another common complaint. Diffi- 
culty in walking, particularly a tendency to deviate to one or the other 
side, occasionally is noted. A tendency to persistent mild somnolence 
or to insomnia occurs fairly frequently but seldom is of severe grade. 
Several cases complained of failing vision and impaired hearing, but the 
fact that many of these patients are of advanced years renders such 
sv^mptoms difficult of interpretation. 

A number of patients have died in the intervening years. Apoplexy 
was by far the most frequent cause of death in these cases. This suggests 
the possibility that the vascular lesions of encephalitis may still further 
weaken the walls of atherosclerotic vessels. 



Differential Diagnosis 

^^'hile we have evidence from our clinical experience that some 
sporadic cases of St. Louis encephalitis undoubtedly occur, the great 
majority of the cases that have been observed have been limited to the 
definite epidemics. The occurrence during the late summer and early 
autumn, at a time when mosquitoes are unusually prevalent, of a con- 
siderable number of cases with fever, headache, somnolence and signs 
of meningeal irritation should suggest the possibility that an epidemic 
of this disease is occurring, Poliomyehtis and the equine types of enceph- 
alomyelitis, however, also must be considered. 

The seasonal incidence, the tendency for many individuals of ad- 
vanced age to be attacked, the high fever and relatively brief course 
with few serious residuals serve to differentiate this infection from 
lethargic (winter) encephalitis of the von Economo type. 

The differentiation from lymphocytic choriomeningitis is more 
difficult. Both may have a prodromal illness. Both have high fever and 
signs of meningeal irritation. St. Louis encephalitis is much more likely 
to occur in epidemics of considerable size, lymphocytic meningitis chiefly 
as sporadic cases. St. Louis encephalitis attacks those of advanced years 
much more frequently. In lymphocytic meningitis the spinal fluid cell 
count in most instances is above 500 cells per cu. mm.; St. Louis enceph- 
alitis shows cell counts usually below 300 cells per cu. mm. Isolation of 

\^OL, M. 750 



82 (6o) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

the \ irus from the spinal fluid should be attempted and sometimes is pos- 
sible in lymphocytic meningitis. In convalescence \irus neutralization 
tests are of value in the differentiation of these infections. 

Eastern equine encephalomyelitis frequently runs a brief course 
to a fatal termination. The course of St. Louis encephalitis, even in 
fatal cases, is likely to be more prolonged. Granular leucocytes usually 
•are quite numerous in the spinal fluid of eastern equine encephalomyelitis, 
rare in the spinal fluid in St. Louis encephalitis. Convulsions are common 
in eastern equine encephalomyelitis, much less common in St. Louis 
encephalitis. The reports, so far available, regarding cases that have 
survived eastern equine encephalomyelitis indicate that serious nervous 
residuals occur; they have been rare in St. Louis encephalitis. Historv 
of exposure to sick horses would suggest the possibility of the equine 
infection, although present evidence would suggest that the intervention 
of the mosquito is necessary in both diseases. History of contact with 
horses is rare in our experience in St. Louis encephalitis. 

The western variety of equine encephalomyelitis appears to resemble 
St. Louis encephalitis very closely in its clinical manifestations. Again, 
the history of exposure to sick horses and mosquitoes should suggest the 
equine infection. The spinal fluid findings may not help greatly in the 
distinction, although the reported average count of 300 cells per cu. mm. 
is distinctly higher than that of St. Louis encephalitis. It is reported that 
children show a considerable number of granulocytes in the spinal 
fluid in the equine infection; these are rare in the St. Louis type of 
infection. Probably the virus neutralization or the complement fixation 
test will be the most reliable method of distinction between these two 
infections. This, however, does not become positive until some time 
after the onset of the illness. 

Cerebral forms of poliomyelitis also may present a problem in dif- 
ferential diagnosis. Children are the ones most likely to be infected with 
poliomyelitis. Nevertheless St. Louis encephalitis does occur in all age 
groups. Virus neutralization tests also may be required for the distinc- 
tion. Muscular palsies are of course rare in St. Louis encephalitis, and 
their occurrance should suggest the possibility of poliomyelitis. 

Treatment 

The treatment of this disease consists of careful nursing with par- 
ticular attention to nutrition during the stage of somnolence and stupor. 
Vol. \^I. 750 



EPIDEMIC SUALMER ENCEPHALITIS 82(61) 

A series consistently handled along these conservative lines presents a 
distinctly low mortality^'. 

Some efforts at reducing intracranial pressure may, perhaps, be 
indicated in cases showing high cerebrospinal fluid pressures. Repeated 
lumbar puncture for this purpose has been advocated by some clinicians. 
Hypertonic glucose or sucrose solutions also found considerable use. 
In stuporous cases the routine emptying of the bladder by catheter 
often was indicated as a tendency to urinary bladder distention was 
observed not infrequently. Feeding by nasal catheter often was neces- 
sary during periods of unconsciousness or where paralysis of the muscles 
of swallowing was noted. 

Convalescent serum or transfused blood has been used occasionally. 
No large series of cases is available for accurate evaluation. However, 
as in other virus diseases it is questionable whether serum can be effective 
after the virus has actually invaded the nerve cells and exists as an in- 
tracellular parasite. In my experience with St. Louis encephalitis virus 
convalescent serum will not protect mice, if the inoculation with virus 
preceeds the administration of the serum. Nevertheless Olitsky and 
Saenz"'"* have reported that enormous doses of hyperimmune serum will 
show some curative effect in western equine encephalomyelitis even 
thoufi^h ijiven subsequent to the virus inoculation. So perhaps the last 
word regarding the use of serum has not been said. 

Animal experiments ^\•ith chemotherapeutic agents such as sul- 
fanilimide, sulfathiazole and sulfadiazine as well as penecillin and 
streptomycin so far have offered no promise that these substances will 
be of value in the treatment of St. Louis encephalitis. An interesting 
observation is that of Sulkin, Zarafonetis and Goth"^ on the beneficial 
effect of ether anesthesia in animals inoculated with various neuro- 
tropic viruses including that of St. Louis encephalitis. This deserves 
further study, 

Webster'" showed that subcutaneous inoculation of mice with living 
St. Louis encephalitis virus for a time protects the brain from infection. 
The development and widespread use of a vaccine against Japanese B 
encephalitis, without serious harmful effects"\ indicates that develop- 
ment of a similar vaccine for use in epidemics of St. Louis encephalitis 
probably would be entirely practicable. However, the irregular nature 
of the outbreaks in any one area and the likelihood that measures for 
mosquito control would be likely to be effective in future outbreaks 
make any widespread use of this type of vaccine at this time unnecessary. 
Vol. VI. 750 



8M62) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\'OUS SYSTEM 

EQUINE ENCEPHALOMYELITIS 

Introduction 

For many years epidemics of encephalitis have been observed among 
horses both in Europe and the United States. The name of Borna 
disease has been given to one type of this infection, and this is 
presumably limited to horses. Two other virus types of encephalitis, 
which cause infection in horses in the United States, are now known to 
infect man. These are known as eastern and western equine encephalo- 
myelitis. The virus causing the infection in the western part of the 
United States was isolated by Meyer, Haring and Howitt-^ in 193 i. The 
same authors reported two cases of encephalitis in men who had been 
in contact with infected horses in California. In 1934 Howitt recovered 
the same virus from the spinal fluid of a man dying from encephalitis 
in the same state and later (1938) isolated the virus from brain tissue of 
a child dying of this disease'"^ 

Eklund and Blumstein'^" reported 6 cases of human infection occur- 
ring in Minnesota in the summer of 1937. Autopsy in one case showed 
the presence of encephalitis. Serum from one case was found to have 
neutralizing antibodies against the western equine encephalomyelitis 
virus when examined by Ten Broeck". 

Kelser'"" in 193 2- 193 3 found that the virus of the western type of 
encephalomyelitis could be transmitted by the Aedes Ae^rypti. Subse- 
quently the same author and also Simmons, Reynolds and Cornell have 
found several other types of the aedes mosquitoes can act as carriers. 
More recently Hammon and Reeves^^" find that Ciilex tarsalis is an 
important carrier of this infection. 

Mcrril, Lacaillade and Ten Broeck'-^ were the first to isolate the 
eastern strain of equine encephalomyelitis virus from horses. Thev also 
have shown that it is possible for this infection to be spread by 
mosquitoes. 

In the summer of 1938 a definite outbreak of encephalitis occurred 
both in horses and human beings in Massachusetts'--'. This was soon 
shown to be due to the virus of the eastern variety of equine encephalo- 
myelitis'^"- "\ 

Therefore, it is now known that both the western and the eastern 
strains of the viruses of encephalomyelitis of horses are pathogenic for 
man. Up to 1942 the geographical dividing line of the distribution of the 

Vol. VI. 750 



EQUINE ENCEPHALOMYELITIS 82(63) 

eastern and western strains of equine encephalomyelitis virus had been 
the Appalachian mountains. Recently a spread of the eastern type to 
Texas has been reported^'". 

Another development in this field has been the isolation of a type 
of equine encephalomyelitis virus in Venezuela which now is known 
to attack man"". 

In Bergey's manuaP^^ this group of viruses is classified as belonging 
to the genus, Erro. Apparently the three types causing human infection 
have not been separated but are given the general designation Erro 
eqiiinus. The virus causing Borna disease in horses, which again is 
serologically different, is designated Erro bornesis. 



Eastern Equine Encephalomyelitis 

Definition. — An acute infectious disease caused by a filterable virus 
characterized by acute onset of fever, headache, delirium and coma. It 
terminates fatally in most cases after a brief course of 3 to 6 days. Cases, 
which survive the acute attack, may have serious nervous residuals. 
Proven human cases so far have been limited to the New England states, 
although the virus has been isolated from horses as far to the southwest 
as Texas"". 



Incidence, Etiology and Epideiniology 

The disease more commonly attacks children than adults, although 
McAdams and Porter^^" have reported an adult case. The seasonal in- 
cidence is identical with that of other late summer types of enceph- 
alitis, occurring chiefly in the months of August and September. 
Preceeding illness such as whooping cough apparently was a predisposing 
factor in several cases. 

Besides the occurrence of this disease in horses it has been shown 
also to occur spontaneously in wild birds, and hence these may act as 
an additional reservoir of infection. In the laboratory the disease has 
been transmitted successfully by mosquitoes^-'' ^"' ^^l Definitely infected 
mosquitoes have not yet been found in areas in which human cases de- 
veloped. Hence the mode of transmission while, presumably from in- 
fected horses and birds by mosquitoes to man, is not fully established. 

In the white mouse, which is quite susceptible to infection with 

Vol. X\. 750 



82(64) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

this virus, the disease is of brief duration. Adequate doses of virus 
usually cause death within 48 hours. According to Webster^^^ monkeys, 
guinea pigs and sheep are quite susceptible also. The rabbit is somewhat 
less susceptible. 



Pathology 

The pathology of eastern equine encephalomyelitis has been de- 
scribed by McAdams and Porter^^'. The meninges show no gross exu- 
date. There is marked engorgement of superficial vessels. The con- 
volutions are flattened and the sulci narrowed. The cut surface shows 
marked congestion particularly of the white matter. The vessels of the 
cerebrum may be more engorged than those of the pons, medulla and 
cerebellum. 

Microscopically there is seen a marked degree of neuronophagia 
throughout the cerebrum. There is also a diffuse infiltration of the 
cerebral tissues with polymorphonuclear leucocytes, monocytes and 
microglia. Some edema and foci of early ischemic necrosis are present 
also. The blood vessels are seen to be distended with erythrocytes. 
Many contain thrombi, some of which are fibrinous and some hyaline. 
Around the vessels are collars of monocytes and polymorphonuclear 
leucocytes. The same type of reaction is present to some extent in the 
pia arachnoid. 

The predominance of polymorphonuclear leucocytes among the in- 
filtrating cells is a point of difference between this disease and St. Louis 
encephalitis. 

Clinical Course 

A typical case develops fever and headache, neck rigidity, delirium 
and coma. Apparently convulsions occur with much greater frequency 
than in other types of encephalitis. The chief additional feature of the 
clinical picture is its rapid progression to a fatal termination. Death 
occurs much earlier than in other forms of encephalitis, occurring usually 
in 4 to 5 days. The immediate mortality is quite high, having been 
around 60 per cent, in the Massachusetts outbreak. 

Vol. \'I. 750 



EQUINE ENCEPHALOMYELITIS 82(65) 

Spinal fluid examination shows an increased pressure and a hio-h cell 
count, varying as a rule between 200 and 1,500 per cu. mm. One feature, 
in which this infection differs from most of the other virus infections 
of the nervous system, is the presence in some cases of large numbers of 
polymorphonuclear leucocytes as well as lymphocytes in the spinal fluid. 
However, Breslich, Rowe and Lehman^"^ have observed high percentae^es 
of granulocytes in the spinal fluid of children infected\vith western 
equine encephalomyelitis. 

Spinal fluid chlorides usually are normal, and the sugar content is 
not decreased. Some increase in protein may occur. Alteration of the 
colloidal gold curve usually is present although irregular in type. In 
the monkey the spinal fluid contains the virus, suggesting the possibility 
of its isolation from this source in man. 

The cases which survive the acute attack usually have shown evi- 
dences of extensive damaije to the nervous system. 



Differential Diagnosis 

The history of exposure to mosquitoes and horses or the occurrence 
of the eastern type of the disease among horses in the same vicinity sug- 
gest the diagnosis in many cases. The sudden violent onset and brief, 
usually fatal course, characterized frequently by convulsions, are valu- 
able diagnostic criteria. The relatively high percentage of granulocytes 
among the leucocytes of the spinal fluid, while bacteria can not be 
demonstrated, is an additional finding which should aid in the differen- 
tial diagnosis. Finally, the isolation of the virus by intracerebral inocula- 
tions of mice with spinal fluid or brain material secured at autopsv^ should 
be attempted. In the convalescent stage a rise in complement fixing and 
virus neutralizing antibodies against this virus in the patient's serum is 
of great diagnostic value. 



Treatment and Prevention 

No known specific therapy is as yet available. The report of Sulkin, 
Zarafonetis and Goth^^^ to the effect that ether anesthesia modifies the 
course and outcome of western equine encephalomyelitis in mice may 
offer a possible approach to effective treatment. The development of 
an effective vaccine such as that used by Beard, Beard and Finklestein'^' 

Vol. VI. 750 



8^(66) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\'OUS SYSTEM 

may be of value in prevention in any future epidemics. Mosquito con- 
trol and isolation of known human and equine cases under conditions in 
which they iire protected from contact with mosquitoes should prevent 
the spread of the disease in times of epidemic, although the reservoir 
among wild birds may be difficult to control. So far the total number of 
proven human cases of this type of infection is small. This is fortunate 
since the mortality is high and the after effects in surviving cases quite 
serious. 



Western Equine Encephylomyelitis 

Defliiition. — An acute infectious disease, caused by a virus and spread 
by mosquitoes. The virus occurs commonly among horses in the western 
part of the United States. Clinically the disease is characterized by an 
acute onset with fever, headache, somnolence, neck rigidity and muscular 
tremors followed in some instances by delirium and coma. The average 
case terminates in from 2 to 3 weeks. The mortality is about 20 per cent, 
or close to that seen in St. Louis encephalitis and distinctly lower than 
that of eastern equine encephalomyelitis. 



Historical Account 

The disease has been known to occur in California since 1931'''^ 
and has been found in man as far east as Minnesota'-"'. A rather large 
outbreak occurred in the late summer of 1938 in North Dakota'"^ One 
of the largest epidemics of encephalitis so far recorded in the United 
States took place in the late summer and autumn of 1941. It was a 
mixed epidemic of western equine encephalomyelitis and St. Louis 
encephalitis. The states of Minnesota, North Dakota, South Dakota, 
Montana and Nebraska were most severely involved, but surrounding 
states were affected also to some extent'^^' ^^''' ^^^' ^^^- ^^^ 



Etiolo(ry iind El')idc7/iioIo(ry 

The earlier reported cases of human infection with the virus of 
western equine encephalomyelitis occurred in individuals who had 
had close contact with infected horses. The more widespread recent 

\'^()i.. \'I. 750 



EQUINE ENCEPHALOMYELITIS 82(67) 

epidemics usually have occurred mixed with St. Louis encephahtis and 
in circumstances which suggest the importance of mosquitoes as the 
transmitting agent of this infection. This has been brought out larc^elv 
through the articles of Hammon and his coworkers""' ^^"' ^^^ in their 
studies of conditions affecting the spread of this disease in the Yakima 
valley of Washington and elsewhere. 

They have been able to isolate the western equine virus from mos- 
quitoes, Ciilex tcirsalis and other species, much more frequently than the 
St. Louis encephalitis virus. Horses are known to be infected in the 
areas in which the disease appears and may serve as the source from 
which human beings are infected. Sulkin"^ has reported the isolation 
of western equine encephalomyelitis virus from chicken mites suggesting 
that chickens may serve as a reservoir of this infection. Hammon was 
unable to isolate this virus from mites"". Hence the method of carry 
over from season to season remains somewhat uncertain. 



Age and Sex Incidence 

The age incidence of this disease appears to be fairly evenly spread 
among the age groups. In California and Minnesota most cases occurred 
in male adults, particularly farmers, who had close contact with horses. 
In North Dakota the cases were divided evenly between the two sexes, 
and some cases occurred among professional workers. The occurrence 
of a case in a nurse, who had taken care of cases of encephalitis, suggests 
the possibility of transfer of infection from one human being to another. 
In general such transfer would appear to be quite rare. 



Fatbology 

Eklund and Blumstein'"'' report the pathological findings in a case 
of western equine encephalomyelitis. In this case there was but minimal 
involvement of the brain tissues, and the most marked lesions were in 
the cervical cord. Brcslich, Rowe and Lehman^"^ in a more extensive 
study of the pathology of this condition found much more involvement 
of the brain. They found definite hyperemia of the leptomeninges with 
flattening of the convolutions of the cerebrum and narrowing of the 
sulci. The brain tissue on cut section was pink. Histologically the 
leptomeninges were infiltrated diffusely with lymphocytes mixed with 

Vol. W. 750 



82(68) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

a few plasma cells and epithelioid cells. Occasionally a few thrombi and 
hemorrhages were seen. Marked perivascular round cell infiltration 
occurred in all parts of the brain, less markedly in the cortex than in the 
basal ganglia, pons and medulla. The cells were mostly lymphocytes 
with an occasional plasma cell, epithelioid cell or polymorphonuclear 
leucocyte. Small aggregations of mononuclear cells, probably of glial 
origin, occurred scattered through the brain. Degenerative changes in 
the nerve cells of the basal ganglia, pons and medulla were seen also. 
Nuclei appeared more deeply stained but indistinct in outline. In some 
instances the nucleus appeared to have disintegrated or completely dis- 
appeared. Foci of demyelination formed a striking^ feature of the 
pathological picture. These foci were found in basal ganglia, pons and 
medulla but not in the cerebral cortex. The brain tissue was replaced 
by a palely staining, spongy, fibrillar mass. These lesions were numerous 
in some cases, rare in others. Marked lesions of the olfactory bulbs 
occurred in two cases, raising the question whether a nasal portal of 
entry might not have been the method of infection in these cases. 



CJ'm'icctl Course 

As in the case of other forms of summer encephalitis the months of 
August and September are the periods of greatest prevalence. The 
clinical picture of western equine encephalomyelitis may closely re- 
semble St. Louis encephalitis"'\ There is usually a sudden onset of fever, 
headache, neck rigidity and mental confusion, sometimes followed by 
delirium and coma. Generalized aching of muscles is common. Nausea 
and vomiting are of frequent occurrance. In children convulsions are 
prone to occur. In those cases, in which drowsiness deepens to coma, 
the mortality is hiq^h. 

Muscular tremors of face and extremities are seen in attempted move- 
ment but usually are absent in repose. Rigidity of the neck and absent 
abdominal reflexes are the most common physical findings. Pathological 
toe signs, such as Babinsky's sign, occasionally occur. The fever rises 
rapidly to levels between ioi° and i05°F.; its average duration is 8 days. 
Chills or chilly sensations may occur with high fever. Death may occur 
as early as 4 days after onset. 

The leucocyte counts of the blood may vary from 5,000 to 22,000 
with an average count of about 12,000. The spinal fluid pressure is 

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EQUINE ENCEPHALOMYELITIS 82(69) 

usually between 10 and 230 mm. of water. The cell count averaq^es 
130 cells per cu. mm., but counts have varied from 2 to 525. The cells 
in adults are about 80 per cent, lymphocytes. In children the percentage 
of granulocytes is higher and may reach 50 per cent. 

The cases reported from California have been fatal cases mostly, 
but in the North Dakota outbreak the mortalitv was approximately 
22 per cent. Cases, which recovered, showed no immediate serious 
nervous sequels. 

Differential Diairj/osis 

Because of the marked similarity of the clinical picture to that of 
St. Louis encephalitis, and because there is evidence that both infections 
may occur in the same area^"\ the differential diagnosis between these 
two conditions is very difficult. The virus neutralization and comple- 
ment fixation tests probably constitute the most valuable method of 
differentiation. It may be well to recall in this connection that Mever^'^^ 
^\•as unable to secure positixc virus-neutralization tests in what he be- 
lieved to be a clinical case. We have no information on the percentage 
of cases that mav^ fail to develop neutralizing antibodies in the blood. 
Isolation of the virus from the brain at autopsy has been accomplished 
by Howitt^"*. So far it has not been isolated from human spinal fluid. 

The differential diagnosis from lymphocytic choriomeningitis may 
be difficult also. Lymphocytic choriomeningitis usually is preceded by a 
well defined, prodromal illness; western equine encephalomyelitis begins 
suddenly. The spinal fluid cell count usually is higher in lymphocytic 
choriomeninfritis. \ irus neutralization and complement fixation tests 
also will aid in this differentiation. 

The seasonal incidence, the definite febrile course of relatively brief 
duration, the rarity of ocular palsies and early recovery without marked 
nervous residuals will serve as a differentiation from the winter, lethargic 
type of encephalitis. 

The presence of a severe epidemic of encephalomyelitis among horses 
of a particular area should Axarn the local medical practitioners that 
human cases of the same infection may occur. 

Prevention and Treatment 

The control of animal epidemics of western equine encephalomy- 
elitis, the isolation of known animal cases, mosquito control and isolation 
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82(70) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\^OUS SYSTEM 

of known cases offer a promising field for preventive medicine. Vac- 
cination of horses against the virus has been tried extensively. 

Beard, Beard and Finklestein^^" have developed and used a vaccine 
containing both eastern and western equine encephalomyelitis virus. 
In human beings it caused no severe reactions and resulted in the ap- 
pearance of virus neutralizing antibodies in the sera of vaccinated in- 
dividuals. They tised formolized chick embryo material as a source 
of virus vaccine. 

No specific therapy has been developed. Treatment is, therefore, 
symptomatic and probably should follow the general lines indicated in 
the section on St. Louis encephalitis. Sulkin, Zarafonetis and Goth'^^ 
have reported modification of the course and outcome of experimental 
infections of mice with western equine encephalomyelitis virus by ether 
anesthesia. This may develop into a possible method of treatment, but is 
still purely in the experimental stage. Hyperimmune serum is of some 
slis^ht benefit early in experimental infections in animals''^^ 

Venezuelan Equine ENCEPHALOMYELnis 

Another type of equine encephalomyelitis has been found to be 
present in several parts of the South American continent"". It has been 
demonstrated in Venezuela, Colombia, Ecuador and the island of Trini- 
dad. The virus has been isolated from animal as well as human sources 
and its serological characteristics studied. The disease is believed to be 
transmitted by mosquitoes and affects men and horses and perhaps other 
large mammals. 

JAPANESE TYPE B ENCEPHALITIS 

Definition. — An acute infectious disease caused by a filteral)le virus 
and occurring in Japan and neighboring areas in the late summer and 
autumn months and exhibiting in most outbreaks a higher incidence and 
mortality with advancing age. Clinically it is characterized by sudden 
onset with fever, headache, somnolence, nuccal rigidity and muscular 
tremors, by moderate leucocytosis in the peripheral blood and pleocyto- 
sis in the spinal fluid with lymphocytes predominating in that fluid. 
The febrile period usually is of 7 to 14 days duration, and convalescence 
is slow. Permanent nervous residuals are rare. 

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JAPANESE TYPE B ENCEPHALITIS 82(71) 

Historical Account 

There is evidence in the Japanese medical literature that a form 
of summer encephalitis has occurred in those islands for many years. 
The disease was first carefully investigated during and after a severe epi- 
demic which took place in 1924. Kaneko and Aoki'\ who studied the 
disease at this time, are responsible for the distinction of this form of en- 
cephalitis from the winter encephalitis described by von Economo^ 
They suggested that winter encephalitis should be called type A and 
summer encephalitis type B. 

After the epidemic of 1924 summer encephalitis has been recosfnized 
as present in Japan in endemic form each year and other epidemic out- 
breaks have occurred in 1929, 1935 and 1937*^ Studies made by Ameri- 
can physicians"^ since the occupation of Okinawa, Japan and Korea in 
1945 indicate the continued presence of this disease in the native popula- 
tion, and some cases have developed in the American forces of 
occupation. 

Geographical Distribution 

Type B encephalitis has been observed to occur in all of the main 
Japanese islands with the exception of Hokkaido. It has been reported in 
the Riu Kiu Islands"^ in Formosa'", Korea, Siberia and possibly in 
China"*^' ^". The greatest incidence has been in Japan between 30° and 
4o°N. latitude, chiefly in districts bordering on the Inland Sea'^ 



Climatic Conditions 

Outbreaks of Japanese B encephalitis are sharply limited to the late 
summer and early fall months of August, September and October and 
end with the onset of cool weather. About 60 per cent, of the cases 
occur in August and 30 per cent, in September, the remaining 10 per 
cent, are found to occur mostly in October with occasional late cases 
in November and early cases in July. Epidemic years are likely to be 
marked by intense heat and scanty rainfall. The Tokyo epidemic of 
1935, however, continued through a period of cool weather'*'. 

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82(72) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NER\^OUS SYSTEAI 

Age and Sex Incidence 

Most of the statistics of the age distribution of Japanese B encephali- 
tis show a marked increase in incidence with advancing age^^ In the 
Tokyo epidemic of 1935 and in cases reported from Formosa and 
Okinawa there has been reported, on the contrary, a high incidence of 
cases among children. Some beHeve that the disease is so mild, when 
it attacks children, that case-reporting is much less complete than in 
adults'^ 

Males are infected somewhat more frequently than females. 



Case Incidence and Mortality 

Although a rather large number of cases have been reported from 
Japan over a period of years, the case incidence per 100,000 population 
has been 20.5 between the years 1924 and 1933 and the death rate 13.3 
per 100,000 population^''. The mortality has varied in epidemic years 
from 42 to 65 per cent. In the Tokyo epidemic of 1935, in which many 
young people were infected, the mortality was lower, being 33.7 per 
cent. 



Etiology and Epidemiology 

In 1934 the virus of Japanese B encephalitis was successfully trans- 
mitted to monkeys by Hayashi"^ In the following year the virus was 
transmitted to mice by Kasahara, Ueda, Okamoto, Yoshida, Hamano 
and Yamada"^. The pathogenicity of this virus for various laboratory 
animals was studied by Webster''", particularly in comparison with the 
St. Louis encephalitis virus. He concludes that the St. Louis virus is 
pathogenic apparently only for mice and Macaciis rhesus monkeys. 
Mice injected with this virus usually show as a first sign of disease tremors 
and convulsions, fail to show virus regularly in the blood stream and 
are resistant to intraperitoneal and subcutaneous injection of all save 
maximum doses. Monkeys injected intracerebrally with massive doses 
are relatively resistant, less than 50 per cent, showing a mild non-fatal 
encephalitis. Japanese virus on the other hand is pathogenic for mice, 
Macaciis rhesus monkeys and sheep. Mice injected with the virus show 

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JAPANESE TYPE B ENCEPHALITIS 82(73) 

paralysis of extremities as a first sign of disease, carry virus in the blood 
stream during the early stages of infection and are relatively susceptible 
to intraperitoneal and subcutaneous injections. Monkeys given an intra- 
cerebral injection of a small quantity of virus develop an acute fatal 
encephalitis characterized by cerebellar incoordination and specific 
necrosis of Purkinje cells. Sheep injected intracerebrally or intranasally 
develop an acute fatal encephalitis but appear to be resistant to sub- 
cutaneous injection. Kasahara^^^ also studied the immunological charac- 
teristics of this virus and regarded it as similar to, but not identical with, 
St. Louis encephalitis virus. 

This virus is now recognized as belonging to the genus Erro and 
has been named Erro japonims-^^. 

The biochemical, biophysical and immunogenic properties of Jap- 
anese B encephalitis virus have been the subject of investigations carried 
out by Duffy and Stanley^^-. They were unable to separate the virus 
from other components of a mouse brain suspension by differential 
centrifugation. A considerable portion of the virus was lost or destroyed 
in the centrifugation process. \\'ith this procedure they were able to 
prepare vaccines of about twice the immunogenic potency of the start- 
ing material, but they did not consider this to be a practical method 
for the preparation of vaccine. The optimal pH range for the activity 
of this virus appears to be near pH 8.5. Ringer's solution, phosphate 
buffer at pH 7.0 and saHne-phosphate buffer at pH 8.2 were poor media 
for the storage of the virus. Most satisfactory as storage media were 
10 per cent, rabbit serum in saline or phosphate buffer 10 per cent, 
skimmed milk in saline or phosphate buffer and i per cent, arginine at 
pH 8.3. Undiluted rabbit serum or undiluted skimmed milk were un- 
satisfactory as storage media. 

Mitamura^^^ and Inada^'^ and other Japanese and Russian investie^ators 
have reported that Japanese B encephalitis virus can be transmitted by 
mosquitoes of two genera, namely Aedes and Cidex. Reeves and Ham- 
mon^'"' confirmed the ability of Aedes and Cidex mosquitoes to act as 
vectors and also incriminated mosquitoes of the genus Ciiliseta. They 
demonstrated transmission by a total of seven species belonging to these 
three crenera. Since the work of Reeves and Hammon was done with 
North American species of mosquitoes, it indicated that, if introduced 
into the United States, danger of transmission of this virus to the popu- 
lation exists in all areas in which these species of mosquitoes are 
prevalent. 

Vol. VI. 750 



82(74) ENCEPHALITIS AND OTHER MRUS INFFX:TI0NS 
OF THE CENTRAL NER\^OUS SYSTEAI 

Pathology 

The pathologv of Japanese B encephalitis has been described by 
L^chiyama^^'^ and Hashimoto^ ''. The chief features are clouding of the 
meninges by serous exudate with some areas of hemorrhagic exudation 
seen occasionally. In some cases considerable numbers of polymorpho- 
nuclear cells \vere present in the meningeal exudate; in others no polynu- 
clears were present. Round cell infiltration was al\\^ays present. 

Areas of focal necrosis M'ere found often, some of microscopic size, 
others easily evident to gross inspection. These lesions were widespread 
in distribution, the anterior commissure, red nucleus, substantia nigra, 
quadrigeminal body, the cortex, the nuclei of the pons and medulla and 
the grey matter of the anterior horns of the cord being common loca- 
tions of the necrotic foci. Some of these were abscess-like areas with 
polymorphonuclear cells, others dense masses of round cells, others 
diffuse areas which might contain round cells, polymorphonuclears, 
rod-like cells and changes in the nerve cells. 

Perivascular infiltrations, mostly composed of lymphocytic cells but 
with a few polymorphonuclears, mononuclears and plasma cells, were 
a marked feature of most cases. They were located in the cortex, the 
walls of the ventricles and the white matter of the hemispheres and cord. 

Sclerosis and calcification of vessels were seen even in young indi- 
viduals. Fresh hemorrhages, usually small in extent, were seen in the 
cortex, white matter and near the anterior commissure. Various types 
of nerve cell degeneration were noted. 

Pneumonia and bronchitis appeared to be present to some extent 
in all cases coming to autopsy. No significant changes were noted in 
other organs. 

Clinical Course 

The incubation period of Japanese B encephalitis has not been 
definitely established. There is frequently an afebrile prodromal period 
of several days duration marked by restlessness, insomnia, headache and 
general malaise'"- '^^- '^^ This is followed by an abrupt onset of fever, 
severe headache, vomiting, somnolence, delirium and coma. Hiccough 
occasionally is present. The maximum temperature usually is between 
1 00° F. and 104° F. The elevation of temperature persists for several 
days and, as a rule, falls by lysis about the 5th or 6th day. Delirium 

Vol.. VI. 750 



JAPANESE TYPE B ENCEPHALITIS 82(75) 

and disorientation commonly are present, and a maniacal state may 
develop. This may be followed by deep coma. Photophobia, nystagmus 
and diplopia may be noted, and various disturbances of speech occur. 
Anuria and constipation are observed frequently as well as urinary and 
rectal incontinence. 

The physical signs commonly seen are rigidity of the muscles of 
the neck and upper extremities. The Kernig sign is positive only occa- 
sionally. Pupillary reactions to light may be sluggish or absent. The 
abdominal reflexes tend to be diminished or absent. Children affected 
by the disease frequently have convulsions. Paralysis of the muscles of 
the extremities often occurs either as a monoplegia or hemiplegia and 
may be of flaccid or spastic type. Transient facial palsy may be noted. 
Bulbar palsy is a frequent cause of death. Pneumonia is mentioned as 
a frequent finding at post mortem examination and may contribute to 
the fatal outcome'*'- "^- '"*• ^'^\ 

Many mild and abortive cases occur particularly in young indi- 
viduals'^' »\ 

LABORAtORY FINDINGS 

The peripheral blood usually shows a moderate polymorphonuclear 
leucocytosis, usually less than 20,000 per cu. mm. The examination of 
the spinal fluid, as a rule, reveals an increase in pressure of 200 to 300 
mm. The fluid ordinarily is clear with a lymphocytic pleocytosis rarely 
greater than 100 per cu. mm."*. Some polymorphonuclears may be noted 
in the fluid close to the onset of the disease. The virus has been isolated 
from the spinal fluid by animal inoculation. It can be recovered still 
more readily from brain tissue of fatal cases. 

A\'ebster'-''' and others'" have shown that the serum of convalescents 
and also of exposed individuals not acutely ill with the disease contains 
neutralizing antibodies against the virus. A complement fixation test 
also has been developed and found to be of practical value in diagnosis"*. 
A rising titre of antibodies against this virus, observed during conva- 
lescence, may be taken as an indication that the preceding infection 
was Japanese B encephalitis. 

Nervous Residuals 

After-effects from Japanese B encephalitis infection are relatively 
uncommon. Neurasthenia and personality changes'" are mentioned as 
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82(76) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERX'OUS SYSTEM 

having been observed. Some persisting paralysis of extremities is noted 
in some cases. Parkinsonism appears to occur very rarely. 



Treatment 

No specific treatment has been developed for Japanese B enceph- 
alitis. Therapy is, therefore, svmiptomatic, once the disease has de- 
veloped. 

Since the disease appears to be spread by mosquitoes, epidemics 
should be controlled by measures designed to eliminate these insects 
and to protect human beings from contract with them. Patients ill with 
the disease should be protected from contact with mosquitoes to pre- 
vent possible ingestion of the virus by these vectors. A vaccine pre- 
pared from infected mouse brains has been prepared and used by the 
U. S. armed forces. Its effectiveness is not fully known at this time"^. 
The preparation and properties of this vaccine have been described by 
DulTy and Stanley^"-. 

AUSTRALIAN X-DISEASE 

An acute infectious disease with the clinical characteristics of an 
encephalitis'^''^ occurred in Australia in 191 7 and 19 18 and possible 
recurrences were noted in 1922"^ and i92 5''\ The outbreaks took place 
during hot weather so that this disease may be classified as one of the 
summer types of encephalitis. It has been gi\en the designation, Aus- 
tralian X-Disease, and, so far as is known, has not spread outside of the 
geographical limits of that island continent. 

\\ hile occurring at all ages up to 68 years, it attacks particularly 
young children under 5 years of age. It is productive of a high mor- 
tality, close to 70 per cent. Death occurs in many cases after an illness 
of but a few days duration. 

A virus Mas isolated during the early outbreaks by inoculation of 
human- brain material into monkeys. Besides for the Macacus rhesus 
monkey the virus was show n to be pathogenic for sheep and also caused 
illness in a calf and a colt. This virus subsequentU' has been lost so that 
its serological relationship to other neurotropic viruses is not known. In 
Bergey's manual"'" it has been classified as a member of the encephalitis 
virus family of Erroiiaceae and given the name Erro hico'^nitiis. 

Vol. Vi. 750 



WEST NILE ENCEPHAIJTIS 82(77) 

Perdrau'^' felt that the pathological lesions produced by the virus 
of Australian x-disease closely resembled those caused by the virus of 
louping ill but felt that no claim could be made that they are one and 
the same virus. Some demyelinization was noted in sections of human 
brain material infected by this virus. Louping ill apparently has not 
been noted in sheep in Australia^'\ 

Clinically the disease is characterized by high fever, mental con- 
fusion, coma, muscular rigidity and convulsions. Serious nervous re- 
siduals, including Parkinsonism, were observed in surviving cases. 



WEST NILE ENCEPHALITIS 

In 1940 Smithburn and his coworkers'^" reported isolation of a neu- 
rotropic virus from the blood stream of a 37 year old woman, a native 
of Uganda, Africa. Little is known of the cHnical manifestations of this 
form of encephalitis, but antibodies against the virus were found in the 
blood of other natives in the vicinity. The virus is pathogenic for mice 
and rhesus monkeys but not pathogenic for African monkeys, guinea 
pigs and hedgehogs. It has been classified"^^ in the genus ''Erro'' and is 
named Erro iiili. 

The virus is of interest in that, while it is a distinct virus type, it has 
some serological relationship to the St. Louis and Japanese B enceph- 



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82(78) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NER\ OUS SYSTEM 

GROUP IV 

Encephalitis and Virus Meningitis With 
Irregular Seasonal Distribution 



LYMPHOCYTIC CHORIOMENINGITIS 

5'}'776>y/}''///5".— Aseptic meningitis, benign lymphocytic meningitis. 

Definition. — x\n acute infectious disease caused by a filterable virus. 
The onset sometimes is sudden but often is preceded by a prodromal 
illness suggesting mild influenza or a gastrointestinal infection. High 
fev'er, severe headache, mental confusion and other evidences of men- 
ingeal irritation develop. The spinal fluid shows a markedly elevated 
count of lymphocytic cells without the presence of bacteria. 

Introduction and Historical Account 

Wallgren^'"' in 1925 described the clinical picture of lymphocytic 
meningitis. The criteria, which he laid down for its diagnosis, are quoted 
by Baird and Rivers'"^ as follows: "sudden onset of meningeal symptoms 
associated with slight or moderate increase in the number of cells espe- 
cially lymphocytes in a bacteria free spinal fluid; a benign course with 
no complications; the absence of foci of acute or chronic infection in 
the vicinity of the brain, for example, sinusitis and the absence from the 
community of diseases known to be capable of producing irritation 
of the meninges". 

These criteria offer little that would difi^erentiate this condition from 
St. Louis encephalitis, western equine encephalomyelitis or any form 
of encephalitis, where meningeal symptoms are prominent. The require- 
ment that diseases, known to be capable of producing irritation of the 
meninjTcs, must be absent from the community, would exclude its recog- 
nition whenever any type of encephalitis is present. 

Many clinicians following these criteria have described many cases 
of "aseptic meningitis" or "lymphocytic meningitis". Baird and Rivers'"* 
have shown that many of these cases give no serological evidence of 
being true cases of lymphocytic meningitis, although the clinical findings 
in some instances may be indistinguishable. Their exact classification 
remains uncertain. 

In the following account the clinical picture as presented is based 

Vol. VI. 750 



LYMPHOCYTIC CHORIOMENINGITIS 82(79) 

on cases in the author's own experience and those found in the litera- 
ture in which either the virus was actually isolated or in which positive 
virus neutralization tests gave suggestive evidence that the cases were 
true cases of lymphocytic choriomeningitis. 

The definite differentiation of lymphocytic choriomenincritis from 
other forms of infection of the central nervous system was established 
through the work of Armstrong and Lillie-". These investigators re- 
ported in 1934 that they had encountered a previously unidentified virus 
in the fifth transplant in monkeys of brain material originally secured 
from an individual who died in St. Louis during the encephalitis epi- 
demic of 1933. They expressed some doubt whether the virus had been 
secured from the original brain material or had occurred spontaneously 
in one of the monkeys used in the inoculations. Later these same authors 
isolated this virus from human brain materials proving its occurrence 
as an infection in man. 

Rivers and Scott^"^ reported in detail two clinical cases in which they 
succeeded in isolating the virus from the spinal fluid. The virus has been 
isolated also from the spinal fluid by Findlay, Alcock and Stern^"*' in 
Ene^land and Broun, Mucther and Greutter have isolated the virus from 
the spinal fluid of a non-fatal case in St. Louis and have serological 
evidence of the occurrence of another case as early as 1932. Traub'"' in 
Princeton, N. J. and Lepine and associates^"* in France have found this 
virus as the causative agent of spontaneous infection in white mice. 

Armstrong, Wooley and Onstott^"^ have studied the virus neutraliza- 
tion tests in serum collected from various parts of the United States. 
Their results indicate that some 1 1 per cent, of the population of the 
country show positive protective power in their serum against this virus. 
Since the number having a history of an acute illness with nervous symp- 
toms is far less than this, they believe that there are many abortive cases, 
and that many other cases occur also in which the manifestations of the 
virus invasion are noted in areas other than the central nervous system. 
Their studies in the monkey indicate that the virus is not strictly neu- 
rotropic but can attack many organs and tissues"". They found that 
children show fewer positive reactions than do adults. 



Geographical Distribution 

There is evidence at the present time that this virus occurs in 
France'"', England'"^ Ireland"' and the United States-". In the United 
Vol. VI. 750 



82(8o) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEAI 

States most of the proven cases have been along the Atlantic seaboard 
or in the Mississippi valley. There is good reason to believe from the 
studies of Amistrong, W'ooley and Onstott"'' that the infection is wide- 
spread. 

Etiology and EproEMioLOGY 

The virus etiology of lymphocytic choriomeningitis has been estab- 
lished by the work described in the previous sections. In Bergey's 
manual'^'' the virus has been classified as belonging to the same genus, 
Le<>;io as the virus of poliomyelitis and has been named Legio erehea. 
The virus is not strictly neurotropic and can be introduced into the 
body by various routes. Armstrong and Wooley found the virus infec- 
tious by urethral and vaginal instillation, suggesting the possibility of a 
venereal mode of transmission. The virus has been found as a spon- 
taneous infection in man, monkeys and mice. It has been experimentally 
transmitted to the guinea pig, hamster, rat, dog, ferret and the chick 
embryo. 

The observations of Armstrong and Sweet"^ and of Armstrong, 
Wallace and Ross"' point to the gray mouse, Miis iinisciiJus, as a reser- 
voir of the disease from which it spreads to man. These observers have 
demonstrated the presence of the virus in gray mice trapped in the homes 
of 4 patients with proved lymphocytic choriomeningitis, residents of 
Washington, D. C. and of one patient in Lancaster, Pa. The probability 
of mice being the source of human infection has been enhanced by the 
study"® of a patient at the Peter Bent Brigham Hospital, Boston, Alass. 
with proved lymphocytic choriomeningitis. This patient had handled 
a male mouse, especially its genetalia, 3 days before developing a sensa- 
tion of feeling tired followed in ten days more by fever, malaise and 
drowsiness. In the home of this individual subsequently mice were 
trapped and the virus of lymphocytic choriomeningitis demonstrated 
to be present in these animals. Dalldorf, Jungeblut and Umphlet"^ 
rccentlv^ have reported multiple human cases in an apartment house 
harboring infected mice in Raleigh, N. C. The virus was isolated both 
from human beings and mice livinsf in this apartment. The human cases 
were spread over a period of several years. 

Armstrong and his associates"* proved that 64 mice from 34 different 
homes in \\ ashino'ton, D. C. were infected of a total of 122 examined 
(52 per cent.); 41 of 62 mice {(i6 per cent.) from 22 homes harboring 
Vol. W. 750 



LYAIPHOCYTIC CHORIOAIENINGITIS 82(81) 

infected mice, when tested, were found to be ininiune to the virus. In 
Washington i out of e\ery 5 mice examined was found to be a carrier 
of the virus. The observations indicate extensive infection of mice with 
the virus of lymphocytic choriomeningitis. 

Traub"' has s1io\mi that an infected mother mouse may convey the 
infection to her offspring and that such congenitally infected mice may 
carry the infection for months. Haas"^ has confirmed at the National 
Institute of Health in \\'ashington the findings of Traub and has shown 
that mice congenitally infected are much more effective transmitters of 
the infection to other mice than are those artificially inoculated. 

These observations point to mice as probable sources of lymphocytic 
choriomeningitis infection in man. Armstrong has suggested that trans- 
fer to man may occur by way of the gastrointestinal tract"' or respira- 
tory tract"^ He believes that the virus escapes from infected mice 
by way of the urine and nasal secretions. The patient at the Peter Bent 
Brigham Hospital"'' suggests that possibly finger transmission may occur 
from virus in the mouse's feces or urine, presumably fing^er to mouth in 
man. If so, then mice can easily infect food with the virus, and by such 
food man can become infected. 

These possibilities, even probabilities, remain, however, as possibili- 
ties, since direct proof is lacking. Laboratory infection of workers 
inoculating and studying vims infected mice is^-"' ^-^- ^" further suggestive 
evidence of the role of mice in the spread of lymphocytic choriomenin- 
gitis in man; Lepine, Mollaret and Kreis^'"^ have produced the disease in 
man by subcutaneous inoculations with mouse viras. Evidence of con- 
tact infection in man is lacking except for that in the Peter Bent Brigham 
Hospital patient as described in preceding sections. 



Pathology 

The pathology of lymphocytic choriomeningitis has been studied 
carefully in the monkey by LilHe"". In this animal are found almost 
constantly irregular, more or less pronounced, lymphocytic infiltrations 
of the choroid plexus of the cerebral ventricles, sometimes accompanied 
by serocellular exudation into the ventricles. Likewise there is an almost 
constant, but moderate, irregularly distributed, lymphocytic infiltration 
of the leptomeninges. Yerv few foci of cellular gliosis and of vessel 
sheath infiltration occur in the brain and cord substance in contrast with 
the picture seen in encephalitis. Meningeal and plexus infiltration may 

Vol. VI. 750 



82(82) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\^OUS SYSTEM 

persist for long pcricxis after infection. Focal lymphocyte infiltration 
and sheath cell proliferation occur in the spinal root ganglia. 

The luniTs often present congestion, serous exudation, interstitial 
edema, hemorrhages and perivascular lymphocytic infiltration. Pyelitis 
and sometimes, hemorrhagic cystitis occurred in a number of animals 
and are characterized by focal and diffuse, mucosal, lymphocytic infiltra- 
tion and edema. Foci of coagulative to fibrinoid hemorrhagic necrosis 
in the liver are seen in about one-fourth of the animals, and focal necroses 
also occur in the adrenals and parathyroid. 

Splenic congestion, a variable grade of bone marrow hyperplasia and 
lymph node follicle hyperplasia and sinus rcticuloendotheliosis are other 
frequent findinq-s. A focal, interstitial, perivascular, lymphocytic infiltra- 
tion is frequent in kidney, epididymis, uterus, fallopian tubes, parathy- 
roid, heart, lung, intestinal mucosa and occasionally, in esophageal 
mucosa, pancreas, adrenal, testes, ovary and skeletal muscles. 

\^ery few fatal human cases have been studied. In one case described 
by Flaymaker and Smadel in a publication from the Army Medical 
Museum there was a severe encephalomyelitis of widespread distribution 
M'ith the brain stem and hippocampus involved most severely. Perivascu- 
lar collars of lymphocytic cells and areas of necrosis, in which many 
o-lial cells had congregated, were prominent features. The vessel walls 
had become hyperplastic. In the hippocampus edema and toxic changes 
in the g-anelion cells were noted. 



Clinical Course 

Baird and Rivers'"^ have published an extensive study of cases of 
lymphocytic choriomeningitis, comparing cases in \\hich the virus has 
been isolated or in \\'hich positive neutralization tests confirmed the 
diaijnosis with other cases in which the diagnosis was made on clinical 
findings alone. 

An interesting^ feature of the clinical course is the occurrence in 
about two-thirds of the proven cases of an influenza-like prodrome. This 
precedes the acute onset by a week or ten days. It is manifested by 
malaise, headache, sometimes coryzal symptoms and mild fever. After 
persistincj one to three days a distinct remission of one to four days 
occurs during^ \\'hich the patient feels well enough to resume his occupa- 
tion. This is followed by the acute onset of meningeal symptoms. Some 

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LYMPHOCYTIC CHORIOMENINGITIS 82(83) 

cases on the other hand begin very suddenly, and no history of such a 
prodromal illness is obtainable. 

The acute phase usually is ushered in with severe headache, fever 
and mental confusion. In some instances abdominal pain, nausea and 
vomiting occur at the onset of this disease. At least one case complained 
of burning on urination suggesting the occurrence of urethritis or 
cystitis. 

Neck rigidity accompanied in most instances by a positive Kernicr's 
sign soon developed. Mental confusion, delirium and coma are seen in 
most cases for varying periods of time. Fever rises to levels of 100° to 
104° F. in most instances, but a few afebrile cases have been reported. 
Hyperactive or hypoactive or unequal tendon reflexes are seen fre- 
quently but are inconstant. Positive toe signs, Babinski's sign, appear 
irregularly in most cases. These are the most common neurological 
findings. 

Findlay, Alcock and Stern"® have reported severe and long persistincr 
muscular palsies in cases observed by them. Transient facial palsies, 
muscular weakness and loss of sensation have been recorded also. 

Most cases recover within about two weeks, although cases have been 
described in which symptoms have persisted for one to two m(H^ths^"^ 
While the mortality probably is low, several fatal cases are included in 
the few definitely proven cases so far studied"". A large number of cases 
of aseptic meningitis have been reported, but as Baird and Rivers"^ have 
shown, it is likely that most of these have been caused by some other 
etiolomcal ag-ent than the virus of lymphocytic choriomeningitis. 



Laboratory Findings 

The urinalysis shoe's in some cases moderate amounts of albumin, 
sometimes with a slic!-ht increase in leucocytes. The peripheral blood, 
as a rule, reveals a slitrht polymorphonuclear leucocytosis with a shift 
to the left in the Schillinq- differential. It should be pointed out that 
granulocytes predominate in the peripheral blood during the same period 
in which the spinal fluid shows a higli count of lymphocytic cells. The 
blood and spinal fluid AA'asscrmann and Kahn tests are not affected by 
this infection in cases so far observed. 

The spinal fluid frequently is under increased pressure. It may be 
clear or turbid depending on the cell count. A positive globulin test 
and a sugar content at the lower limits of normal, i.e. between 45 and ^^ 

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82(84) ENCEPHALITIS AND OTHER MRUS INFECTIONS 
OF THE CENTRAL NER\'OLS SYSTEM 

mgiii. per 100 c.c, usiuilly are found, but the marked reduction in sugar 
content seen in tuberculous and other bacterial forms of meningitis has 
not been observed here. The chloride content of the spinal fluid likewise 
is at the lower limits of normal. Ihe cell count is above 300 per cu. mm. 
in the vast majority of cases and above 1,000 per cu. mm. in about one- 
half of the known cases. Ihe average is, therefore, distinctly higher than 
in most cases of encephalitis. The differential count on the spinal fluid 
shows in most instances between 90 and 100 per cent, of lymphocytic 
cells. 

The colloidal gold reaction usually show^s some alteration from the 
normal, but w'idely different types of curves have been reported in dif- 
ferent cases. A curve resembling that of tabes dosalis is perhaps the 
most common. 

The fluid shows no bacteria in smear or culture. Inoculation of the 
fluid intracerebrallv into white mice has resulted in the isolation of the 
virus in a number of instances. The animals become sick and die about 
the seventh to eighth day as a rule. Guinea pios and monkeys also are 
susceptible. Such is the clinical picture and laboratory findings of the 
typical severe case. 

There are cases on record, \\'here no menincreal symptoms were noted 
but merely a history of "grippe", and yet following this neutralizing 
antibodies against the virus of lymphocytic choriomeningitis were found 
in the patients' serum. This shows that abortive cases of obscure symp- 
tomatology undoubtedly occur. The high percentage of sera in the 
general population, which neutralize the vims, far outnumbering known 
cases with meningeal symptoms, is further evidence for the existence 
of these abortive cases. 

Differential Diagnosis 

It is obvious that this infection can be easily confused with tubercu- 
lous meningitis and with cases of encephalitis in which meningeal symp- 
toms are prominent. 

In cases of tuberculous meningitis, where tubercle bacilli are found, 
the differentiation is, of course, easy. \\'here the bacteria are so few as 
to escape detection, the following differential points are to be kept in 
mind. 1 he spinal fluid in tuberculous meningitis usually shows a dis- 
tinctly reduced chloride and sugar content. It also, as a rule, shows a 
consitlerable admixture of poUniorphonuclcar leucocytes with the lym- 

\'()i.. \'l. 750 



LYMPHOCYTIC CHORIOMENINGITIS 82(85) 

phocytes in cases where the cell count is high. Cases with low cell 
counts, however, may have a pure lymphocytic picture as does lympho- 
cytic meningitis. The outcome of tuberculous meningitis has been 
practically universally fatal; most cases of lymphocytic choriomenin- 
g-itis recover. 

The diiferentiation of lymphocytic choriomeningitis from cases of 
St. Louis encephalitis certainly is extremely difficult. It is true that the 
average age incidence differs in that young adults are attacked most 
frequently by lymphocytic choriomeningitis and those of advanced 
years are most susceptible to St. Louis encephalitis. However, both 
diseases can occur at any age period. The seasonal incidence of St. Louis 
encephalitis is limited very largely to the months of August, September 
and October. Lymphocytic choriomeningitis seems most common in 
the autumn and spring months but has been reported in all seasons. 

The clinical picture and laboratory findings of St. Louis encephalitis 
and lymphocytic choriomeningitis may be highly similar. In general, 
however, most cases of lymphocytic choriomeningitis show spinal fluid 
cell counts above 300 per cu. mm.; the vast majority of cases of St. Loui"? 
encephalitis have cell counts below 300. Here again, however, there is 
definite overlapping in exceptional cases. 

The isolation of the virus from the spinal fluid has been accomplished 
several times in the case of lymphocytic choriomeninci^itis. It has not 
been accomplished so far in cases of St. Louis encephalitis. 

A'^ims neutralization tests and complement fixation tests are the most 
reliable methods of differential diagnosis provided that specimens of 
serum are collected at proper intervals to reveal the rise in antibodies 
durinq- convalsecence. Smadel, Baird and Wall"^ have reported on the 
use of the complement fixation reaction in lympocytic choriomeningitis. 



Treatment 

No specific treatment is available as yet for this infection. Cases 
require careful nursinij particularly during periods of delirium and coma. 
Maintenance of adequate nutrition by feeding through nasal catheter 
may become necessary. Intense headache may require relief by use of 
salicylates, codeine or morphine or some of the more recently developed 
analgesics. 

Lowerincr of the pressure of the spinal fluid by puncture and with- 
drawal of fluid seem at times to relieve headache and to make the patient 

Vol. y\. 750 



82(86) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\'OLS SYSl EM 

more comfortable. Hypertonic glucose or sucrose given intravenously 
may be of value for their effect in lowering spinal fluid pressure. 



LOUPING ILL 

Louping ill is an infection involving the nervous system and caused 
by a filterable virus which is endemic in sheep in Northern England and 
Scotland. Infection of shepherds by this virus has not been reported, 
but human infection has occurred in laboratory workers in several in- 
stances'^ Since these cases had no particular seasonal incidence, it 
appears proper, for the time being, to list this infection among those 
with indefinite seasonal distribution. However, the close serological 
relationship between the virus of this disease and that of Russian spring- 
summer tick borne encephalitis must not be forgotten"^^ This relation- 
ship is particularly close in the cases of encephalitis appearing in Euro- 
pean Russia'"^^ 

The virus of louping ill is classified as belonging to the viruses of the 
Ijenus Erro and is termed Erro scot'icits-^^. Besides sheep and man, 
monkeys, mice, rats, horses, cattle and pigs have been found to be 
susceptible to infection by this virus. In sheep the transmission from 
animal to animal probably is by the bite of ticks, resembling in this 
respect Russian encephalitis. All proven human cases, however, have 
occurred as accidental laboratory infections. 

^^'hile one case, believed to be due to this vims, had symptoms 
resembling;- an influenzal infection, others had definite encephalitic symp- 
toms. In these cases a prodromal period of several days duration oc- 
curred, characterized by fever, headache and malaise. This M-as follo\\'ed 
by a sudden increase in the severity of these symptoms as well as the 
appearance of sis^ns of meningeal irritation. Diplopia, blurring of vision 
and photophobia, various cranial nerve palsies and changes in deep and 
superficial reflexes occurred. 

The sninal fluid showed an increased cell count ^^'ith mononuclear 
cells predominating. There was a slight polymorphonuclear leucocytosis 
in the peripheral blood. 

Diagnosis \\as established by the appearance of virus neutralizinij 
antibodies aijainsr the virus of louping ill in the blood serum of these 
patients during convalescence. 

All cases eventually recovered m ithout nervous residuals. 

\o\.. W. 750 



BIBLIOGRAPHY 82(87) 

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82(94) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NERVOUS SYSTEM 

109. ARiMSTRONG, C, WOOLEY, J. and ONSTOTT, R.: Distribution 
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139. MEIKLEJOHN, G. and HAALMON, W. AIcD.: Epidemic of en- 

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Post-iiifcctioi/s Encephiilitis: Gencrcil Discussion 

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Vol. VI. 750 



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Alultiple cases of Choriomeningitis in apartment harboring infected 
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239. OLITSKY, P. K. and SAENZ, A. C: Serum treatment of ^\■estern 

equine encephalitis in mice determined by the course of viral infec- 
tion. Proceed. Soc. Evp. Biol, and Aled., 1948, LXVIII, 200. 

240. SAIITHBURN, K. C, HUGHES, T. P., BURKE, A. W. and PAUL, 

J. H.: A neurotropic virus isolated from the blood of a native of 
Uganda, Am. Jour. Trop. Aled., 1940, XX, 471. 

241. BERGER, F. AL and SCHWARTZ, R. P.: Oral '^myanesin" in treat- 

ment of spastic and hyperkinetic disorders. Jour. Am. Aled. Assoc, 
1948, CXXXVII, 772! 

242. PHILIP, C. B., COX, H. R. and FOUNTAIN, J. H.: Protective anti- 

bodies against St. Louis encephalitis virus in serum of horses and 
man, Pub. Health Rep., 1941, LVI, 1388. 
Vol. VI. 750 



84(2) ENCEPHALITIS AND OTHER VIRUS INFECTIONS 
OF THE CENTRAL NER\^OUS SYSTEM 

243. HA.MAION, W. AIcD., REEVES, W., BRENNER, S. and BROOK- 

MAN, B.: Human encephalitis in the Yakima valley, Washington, 
1942, Jour. Am. Med. Assoc, 1945, CXXVIII, 1 133. 

244. HAMMON, W. McD.: Eastern and western equine encephalomyelitis 

and the St. Louis type as observed in Washington, Arizona, New 
Mexico and Texas, Jour. Am. Med. Assoc, 1943, CXXI, 560. 

245. CASALS, J. and PALACIOS, R.: Complement fixation in encephali- 

tis and rabies virus infections. Science, 1941, XCIII, 162. 

246. IKEI, S.: Experimentalle Studien iiber das Entstehungsmoment der 

Postvaccinal-encephalitis, Japan. Jour. Exper. Med., 1932, X, 563. 

247. HIRST, G. K.: The quantitative determination of influenza virus and 

antibodies by means of red cell agglutination. Jour. Exp. Med., 
.94^^ I XXV, 49. 

July I, 1950. 



Vol. M. 750 



CHAPTER III-A 
POST-VACCINAL ENCEPHALITIS 

By a. H. GORDON 

Table of Contents 

Incidence 84 (3) 

Clinical Features 84 (4) 

Illustrative Cases 84 (4) 

Pathology 84(7) 

Relation to Vaccination 84 ( 1 1 ) 

Etiology 84(13) 

Treatment 84(14) 

Prevention 84(15) 

Bibliography 84(15) 

Incidence 

The history of post-vaccinal encephalitis as a clinical entity does not go 
back more than two decades. Occasional complications in the central nervous 
system following vaccination had been noted from time to time, and some of 
these had been diagnosed as tetanus and quite possibly some of them were, but 
in 191 2 Turnbull and Mcintosh recorded the first case of post-vaccinal encepha- 
litis from the London Hospital and between 191 2 and 1923 reported six other 
cases. 

From 1923 to 1927 in the Netherlands 139 cases of disease of the central 
nervous system following vaccination had been described of which 41 died. In 
England the RoUeston committee on vaccination reported 25 cases of acute 
nervous disease occurring within four weeks of vaccination between January i, 
1926 and September 30, 1927. Up to May 1929 it was estimated by Jitta that 
the total number of cases recognized in Holland was 146 and up to September 
1929, 115 cases had occurred in England. 

In Germany up to the same date 67 cases had occurred. In Austria 81 
cases, in France 5, while Belgium, Spain, Greece and Italy reported no cases. 
Norway had 28 cases, Poland 2 cases, Sweden 16 cases. The Soviet republic 
reported 2 cases and Jugo-Slavia one case. Asia and Africa reported no cases. 

For the United States there is a record of 71 probable or proven cases of 

Vol. VI. 233 

84(3) 



84 (4) POST-VACCINAL ENCEPHALITIS 

post-vaccinal encephalitis for the ten years prior to 1932, including 22 cases 
recorded for 1930 and 8 cases for 1931. In Canada no cases had been re- 
ported up to 1930, but two cases are now on record. 

Clinical Features 

The clinical features of the disease form a fairly constant picture, and while 
there is still difference of opinion as to the essential nature and direct cause of 
the processes involved, there is a notable constancy in the manner of onset 
and the course of the symptoms. 

The onset is sudden and stormy with headache, vomiting, fever and often 
convulsions. Paralysis and coma are frequent. Meningeal signs and cranial 
nerve palsies are commonly present, while the cerebrospinal fluid is remarkable 
for its slight departures from the normal. Globulin may or may not be in- 
creased. The cells are not usually increased greatly in number and the pressure 
is not elevated. 

Illustrative Cases 

The following two cases illustrate the clinical features: 

Case I. A boy aged 11 years, who had been well and strong up to the onset 
of this illness was brought into the Montreal General Hospital unconscious on 
August II, 1928. 

He had mumps, measles and chickenpox in infancy; otherwise his history 
was negative. 

The parents stated that he had been suddenly seized with a severe headache 
on a Sunday night and that this had continued throughout Monday and 
Tuesday and was accompanied by vomiting. On Wednesday morning he be- 
came unconscious and was brought to the hospital. 

When seen he could be partially aroused but would not answer questions. 
He lay on his left side with his head bent forward and both hips and knees 
flexed. He was restless and every 5 minutes or so would throw himself about in 
bed. 

The pupils reacted sluggishly to light, the left was somewhat dilated, and 
there was ptosis of the left eyelid. 

The eyes were kept partially open and responded but little to stimuli. 
There was no disease found in the ears or in the mastoid regions, and there was 
no sign of head injury. The ocular fundi were normal. 

There was some spasticity of both arms and legs, the neck was somewhat 
rigid and Kernig's sign was slightly present. The al^dominal reflexes were 
absent, the knee jerks were present and a well defined bilateral Babinski 

Vf)i.. VI. 233 



CLINICAL FEATURES 84 (5) 

phenomenon was elicited. On the following day the knee jerks could not be 
obtained. 

There was incontinence of both urine and faeces. 

On admission there was herpes on both lips. The pulse rate was 90, the 
respirations 16 and the temperature which was 100.2° F. on admission, rose 
steadily to 107° F. before death two days later. 

The right arm and leg developed a marked degree of spasm and a lateral 
nystagmus appeared. Later the spasm passed into flaccidity and complete 
unconsciousness developed. 

Respirations became more rapid and dulness and rales appeared at the bases 
of both lungs. For some time before death the head and eyes were turned toward 
the right and both pupils became much contracted. 

Lumbar puncture on two occasions gave a clear fluid not under tension, 
containing no cells and only a faint reaction for globulin and a negative reaction 
for sugar. Culture of the fluid was negative. 

Blood examination showed hemoglobin 75 per cent., red cells 4,800,000, 
leucocytes on three counts, 8000, 7700 and 7800 per cu. mm. 

Vaccination history. — The family had recently removed from another 
Province, and as the child had not been vaccinated, he could not enter school. 
Twelve days before the onset of the illness, vaccination by the scratch method 
was done in one area on the left arm. 

On admission the scab, which was hard and dark brown, was about 2 cm. in 
diameter, with quite marked redness and induration about it. The left axillary 
glands were enlarged and tender. 

The progress notes upon the case are of interest. On the day of admission 
the following note was made: "The case has all the appearances of a meningeal 
reaction, but the character is hemiplegic, and the predominance of weakness 
over rigidity is noticeable. This, with the practically negative spinal fluid, 
suggests some unusual cerebral infection and vaccinia is suggested." 

The diagnosis made shortly before death was as follows: "Some type of 
spreading encephalitis; poliomyelitis superior is suggested, with the predominant 
lesion in the left cortex. Terminal bronchopneumonia. The terminal myosis 
and fixed pupils suggest a basal lesion." 

Necropsy. — A very limited post-mortem examination was performed 2^ 
hours after death. Permission could not be obtained to examine the brain. 
The spinal cord could be examined only from the third cervical to the lumbar 
region. 

Many microscopic sections were examined from various areas in the cord. 
The following is the histologic report upon them. 

"Some of the sections show a quite normal condition; the neuroglia is 
intact; the vessels are normal; the nerve cells, dendrites and nerve fibrils are 

Vol. VI. 233 



84 (6) POST-VACCINAL ENCEPHALITIS 

well preserved. There are areas in the cord, however, which show lesions of 
varying intensity in the cord substance. There are numerous areas, more 
marked in one half of the cord than in the other, where demyelinization is very 
prominent. These areas appear as discrete and confluent patches. In the 
discrete areas one notes that this lesion occurs as a ring-Uke area about a blood 
vessel. The demyelinization is more marked throughout the anterior portion of 
the cord than in the posterior portion. In some of the sections a similar lesion 
is seen along each side of the anterior commisure as a zone of varying length 
and breadth. As a whole, there is not much cellular infiltration of the demye- 
linized areas. In certain places, however, these areas do show quite a marked 
infiltration with cells." 

The other organs of the body showed no gross lesion except in the lungs, 
where congestion and areas of acute bronchopneumonia were found. 

Microscopically, there was a general vascular congestion of the kidneys, 
particularly marked in the medulla. The convoluted tubules showed cloudy 
swelling. 

Sections of the excised vaccination area showed superficial ulceration and a 
scab consisting of necrotic material. Extending through the skin and into the 
subcutaneous tissue there was a diffuse inflammatory exudate with necrotic 
foci. The cellular exudate was composed of lymphocytes, plasma cells, endo- 
thelial cells and enormous numbers of eosinophils. 

Case 2. A man of 24 years of age, who had three times been vaccinated, 
but in whom vaccination had never "taken" and who showed no scar, was 
vaccinated again on January 21, 1932 by a physician of the Board of Health. 

Three days later his arm became very sore and inflamed and on January 
27, six days later, he suddenly developed headache and photophobia, vomited 
repeatedly and could not sleep. 

He was seen by Dr. W. R. Kennedy who found marked retraction of the 
neck and slight temperature and did a lumbar puncture. The fluid returned 
clear with an increase of globulin but no increase of cells. In view of the history 
and the findings, he made a diagnosis of post- vaccinal encephalitis, and the 
man was admitted to the Montreal General Hospital. The pulse was 84, 
temperature 99.2° F., blood pressure 140/100. 

The head was drawn back and the neck rigid, and there was a marked 
Kernig reaction. The pupils were even and reacted to light. There was a 
lateral nystagmus on looking to the right, but there was no ocular palsy. There 
was soreness in the muscles of mastication, and he objected to opening his 
mouth which raised the suspicion of tetanus. 

There was distinct weakness of the lower left face with loss of sensation 
and later weakness of the left arm appeared. The left abdominal reflex was 
diminished. The ocular fundi showed no change. 
Vol. VI. 233 



PATHOLOGY 84 (7) 

Headache disappeared at the end of the first week but reappeared for a time 
after several day's absence. 

Blood examination showed red cells 4,400,000, leucocytes 6,400, Hg. 90 per 
cent., polynuclears 57, lymphocytes 38, mononuclears 4 per cent. 

Lumbar puncture was done on six occasions. Globulin was constantly 
present. Total protein .075%. Sugar .061. The cells averaged 10, chiefly 
mononuclears. The pressure ranged from 80 to 130 mm. water. 

The blood Wasserman, the spinal fluid Wasserman and the colloidal gold 
reaction were negative. Blood cultures and culture from the cerebrospinal 
fluid were negative. 

On admission the blood sugar was .135 and dropped to .117 at discharge, 
and twice during his illness sugar was found in the urine. He was given daily 
on three successive days 20 c.c. of serum from recently vaccinated persons. 

The temperature fell to normal on the loth day of the illness, and the pa- 
tient was discharged well in four weeks with slight left facial weakness and de- 
viation of the tongue to the left as the only residual sym.ptoms. 

Two rabbits were given intracerebral inoculations, one with 3 c.c. of cere- 
brospinal fluid from this case and the other with vaccine virus in saline solution. 
Both animals survived. The one inoculated with cerebrospinal fluid from the 
patient showing no illness, the one inoculated with vaccinia virus becoming ill 
for a few days. 

Pathology 

The lesions found in post-vaccinal encephalitis fall into the category of non- 
suppurative diseases of the central nervous system, among which are also in- 
cluded encephalitis lethargica and poliomyehtis. While all three show some 
resemblances, they also have marked differences in their histological appear- 
ances. 

With the encephalitis associated with measles, variola, anti-rabies inocula- 
tion, Schilder's disease and possibly influenza the post-vaccinal process has a 
marked resemblance and some claim an identity. 

TurnbuU and Mcintosh sum up the matter by stating that the characteristic 
features of the inflammation of the central nervous system in post-vaccinal 
encephalitis are the number and size of zones of extra-adventitial perivascular 
infiltration in contrast to the development and size of the adventitial vascular 
sleeves; the obvious perivascular distribution of the infiltrations; the conspic- 
uous zones of softening with relatively little cellular infiltration that surround 
vessels in the white matter; the large extent to which the white matter is 
involved although the involvement of the gray matter is absolutely greater; 
the extensive involvement of both cerebral cortex and spinal cord ; the incidence 

Vol. VI. 233 



84(8) POST-VACCINAL ENCEPHALITIS 

of the maximal inflammation upon the lumbar and upper sacral cord and the 
pons, and the close similarity in the t\-pe and incidence of the inflammation in 
all cases. The most characteristic histological feature is the zone of perivascular 
softening in the white matter. 




P'iG. I. — Encephalitis Lethargica. Broad lymphatic collar about 
a small cerebral vessel. 

There are certain aspects of the microscopic lesions of poliomyelitis, post- 
vaccinal encephalitis and encephalitis lethargica that are similar, yet there are 
certain lesions which seem to differentiate these three diseases. The accom- 
panying iUustrations demonstrate especially these differentiating features. 

Fig. I, is from a clinical case of encephalitis lethargica. It shows a blood 
vessel dilated with blood. About it is a very distinct encircling zone infiltrated 
with cells, most of which are of the lymphocytic series. The slide shows this 
alone. None of the areas of softening that have been described in encephalitis 
lethargica are present. Perivascular lymphocytic collars are not diagnostic 
of encephalitis because they appear in other acute diseases of the central nervous 
system, one of which is post-vaccinal encephalitis. 

Fig. 2, is from a clinical case of anterior poliomyelitis. The microphotograph 

Vol. VI. 233 



PATHOLOGY 84 (9) 

is taken so as to include a portion of the anterior horn and the adjacent white 
matter. One intact motor nerve cell and the sites of two others are seen. The 
latter areas contain numerous phagocytic cells, which have almost completely 
removed the two nerve cells that have been destroyed by the virus of polio- 





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Fig. 2. — Anterior Poliomyelitis. Portion of anterior horn with 
adjacent white matter to show one nerve cell intact; the sites to two 
others are represented by great numbers of phagocytic cells. Note the 
absence of demyelinization. 

myelitis. There is no demyelinization. This lesion has not been described in 
association with post-vaccinal encephalitis. 

Fig. 3, is from the first case of post-vaccinal encephalitis. This shows the 
microscopic lesion which is said to be characteristic of the disease, areas of 
demyelinization. In this particular case these areas are more numerous in one 
half of the cord, are discrete and confluent, and in the centre of some of them a 
dilated and engorged blood vessel is distinctly seen. 

Fig. 4, from the same case and near the same site as Fig. 3, shows very 
marked demyelinization and like the former slide there are dilated vessels with 
areas of demyelinization about them. 

Vol. VI. 233 



84 (lo) POST- VACCINAL ENCEPHALITIS 

Fig. 5, also from this case of post- vaccinal encephalitis, is a high power 
photograph of a small area of demyelinization in the gray matter. It shows 
infiltration of an area of demyelinization with cells. 

Figs. 3, 4 and 5 demonstrate the microscopic lesions which are claimed by 
TurnbuU and others to be characteristic of post-vaccinal encephalitis. 




Fig. 3. — Post-vaccinal Encephalitis. To illustrate areas of 
demyelinization, in the centres of some of which a widely dilated blood 
vessel is seen. 

Microscopically the general character of the lesion of post-vaccinal encepha- 
litis is that of a meningo-encephalitis. The meninges are infiltrated with small 
lymphocytes, plasma cells and large cells of endothelial origin. While the 
meningitis is slight, it can be traced down over the cord. 

Infiltration of the perivascular space, the so-called lymphocytic collar or 
sleeve of the type seen in epidemic encephalitis, is the commonest lesion present, 
but this feature is shared with both epidemic encephalitis and poliomyelitis. 
The striking feature of the post-vaccinal disease is the presence of areas of 
demyelinization extending for some distance around the vessels and unassociated 
with vascular thrombosis. Demyelinization is an essential feature of the extra- 

VOL. VI. 233 



RELATION TO VACCINATION 84 (n) 

adventitial softening, and the lesions have the punched out appearance of those 
in disseminated sclerosis. Thus demyelinization appears to be the primary 
lesion and cellular infiltration is secondary. 



Fig. 4. — Post-vaccinal Encephalitis. Transverse section of cord 
showing demyelinization most marked throughout one-half of the cord. 



Relation to V.accination 

In the 90 English cases the period elapsing between the date of vaccination 
and the onset of encephalitis was in 81 cases from the 7th to the 15th day, 
with the greatest number on the 12 th day. Eight cases appeared up to the 6th 
day and one on the 23rd day. 

In this group of 90 cases collected by the Committee on Vaccination in 1927 
and 1928, there were 42 deaths, of these 41 occurred within 3 weeks of the 
onset. 

Two thirds of the cases were of school age, and all the vaccinations were 
primary except in 3 of the 90 cases. The age group from 4 years to 15 years 
furnished 68 cases or 75 per cent. 

Of the 41 fatal cases in this group 31 or 75 per cent, occurred in the same 

Vol. VI. 233 



84 (i2) POST-VACCINAL ENCEPHALITIS 

age group of 4 to 15. In this whole group of 90 cases, no case occurred in the 
period up to one year of age. 

In the Bulletin of the OfBce International d'Hygiene Publique of 1930, 





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Fig. 5. — Post-vaccinal Encephalitis. Cellular infiltration in an 
area of demyelinization. High power. 

XXII, which is a report of the Smallpox and Vaccination Commission, the 
figures relating to the disease in the Netherlands are in general similar to the 
English statistics. Eighty three cases of encephalitis following vaccination are 
tabulated of which 52 occurred after primary vaccination and 31 after re- 
vaccination. Of these attacked after primary vaccination 14 died or 26.9 per 
cent. 

On an average the symptoms appeared on the nth or 12th day, while after 
revaccination the average onset was on the loth day but sometimes even on the 
2nd day, and on the average, death occurred on the 5th day. 

It was calculated that one case of encephalitis occurred in every 2,300 pri- 
mary vaccinations and one in every 50,000 revaccinations. One case occurred 
among 3,487 children vaccinated between i and 2 years of age, and one case in 
every 815 primary vaccinations between 6 to 11 years, and though 16,000 

Vol. VI. 233 



ETIOLOGY 84 (13) 

vaccinations had been done in children under one year, no cases of encephaUtis 
had occurred. 

In this connection it should be noted that T. F. McNair Scott reports a case 
in a child of 6 months occurring 10 days after vaccination and recovering in 16 
days. He also reports 21 other cases from various sources, but many of these 
vary from the usual picture of the disease both in time of onset and clinical 
course, so that one must still regard vaccinal encephalitis as excessively rare in 
infancy. 

A study of combined statistics would justify the broad statement that post- 
vaccinal encephalitis is in general a disease following primary vaccination in 
children between 6 and 12 years of age. 

The relation of the onset of encephalitis to the number of insertions and to 
the intensity of the vaccination reaction is not easy to determine. 

The great majority of the English cases followed vaccination in 4 insertions, 
but as the Rolleston report comments, there were more vaccinations in four 
insertions than in 3, 2 and i insertions combined, but it is of interest that in 
1929 public vaccinators were ordered to make one insertion only. 

The same uncertainty holds as to the relation of encephaUtis to the intensity 
of the vaccination reaction, though a perusal of case reports indicates that 
severe reactions have been common events in those stricken by encephaUtis. 

Etiology 

Many questions remain to be answered in reference to the disease as a whole 
and the problem is well presented by TurnbuU and Mcintosh. 
They state that three possibilities appear: 

1. That vaccination provokes a virus already present in the body. The 
presence of almost identical findings in the nervous system in measles, smaU- 
pox, anti-rabies inoculation, etc., would offer some support for this view. 

2. That the vaccination lymph is contaminated. 

3. That some other virus contaminates the vaccination wound. 

The fact that the disease has followed vaccination with lymphs from various 
sources in the same epidemic is an argument against the two last views. 

Their conclusion is that the clinical and histological features of the disease 
are so constant that there can be little doubt that vaccination is not a coinci- 
dence but a cause of the encephalitis. 

In this connection it may be noted that Aldershoff of HoUand puts forward 
the view that a monilia, often found in the throats of cases of encephalitis and 
of poUomyelitis as weU as in the throats of contacts, may be the responsible 
virus. 

From the standpoint of epidemology there is no correlation between the 

Vol. VI. 233 



84 (i4) POST- VACCINAL ENCEPIL\LITIS 

incidence of this disease and the incidence of encephalitis lethargica or of 
poUomyehtis, but there is a direct correlation between it and the number of 
cases of smallpox and the number of charges of vaccine lymph distributed by 
the Health Boards. 

All attempts have so far failed to reproduce encephalitis in animals by the 
injection of material from the brains of those dying of the disease. 

In spite of this Hekman of Rotterdam is unwilling to admit that an unknown 
virus is responsible for the disease and strongly upholds the view that vaccinia 
alone is the responsible agent, and he supports this view by reports of ii cases 
of encephalitis following vaccination and 2 following revaccination which were 
treated by the injection of blood serum from recently vaccinated persons. Of 
these 13 cases 11 recovered. 

Netter strong!}- supported Hekman's views and on this basis also Professor 
Paschen, Director of the Vaccination Institute of Hamburg, arranged for the 
collection of blood from recently vaccinated nursing students for the early 
treatment of cases of post- vaccinal nervous disease. 

Unknown to Hekman at the time, Sir Thomias Horder in London had 
reported a case of vaccinal encephalitis treated successfully at St. Bartholo- 
mew's Hospital by intrathecal injection of serum from the patient's mother who 
had been recently vaccinated. 

Treatment 

The treatment of post-vaccinal encephalitis should follow the lines em- 
ployed in other forms of encephalitis. Lumbar puncture repeated daily if need 
be has justified itself, and in the second of our cases it gave so much relief to 
the headache that the patient himself requested it. 

Sedatives as codein and morphin may be required, and quiet and relative 
darkness help to make the patient comfortable. 

While by some regarded as empirical and by others as valueless, the injection 
of the serum of recently vaccinated persons, particularly those vaccinated by 
the same type of vaccine, has a reasonable basis, and in view of Hekman's 
results is amply justified. It may be given intravenously or intrathecally in 
doses of 10 to 50 c.c, daily. 

Where time is a factor, and no such prepared serum is available, the in- 
tramuscular injection of the donor's citrated whole blood may be employed. 
It should be given at the very first appearance of central nervous symptoms 
which appear within the incubation period of post-vaccinal encephalitis. 

In larger institutions a supply of serum might be obtained from recently 
vaccinated people such as entrants into the schools for nurses, after the plan of 
Paschen. 

Vol. VI. 233 



BIBLIOGRAPHY 84 (15) 

This continent has had its occasional cases, and with a large unvaccinated 
population the appearance of an epidemic of smallpox or a smallpox scare, which 
would lead to mass primary vaccination at the susceptible age periods, might 
readily duplicate the experience of the European countries, with regard to post- 
vaccinal encephalitis. 

Prevention 

In the matter of prevention, it is beyond argument that in Europe it is the 
countries in which early vaccination has not been compulsory which have 
suffered most from this disease. 

Whatever arguments there may be about the exact nature of the infecting 
agent, there is no argument about the fact that the disease is a rarity in children 
vaccinated under one year of age. Therefore the first step toward prevention is 
early vaccination. 

The Rolleston Commission was sufficiently impressed by the greater danger 
of encephalitis in those vaccinated by four insertions to recommend that only 
one insertion be employed, and this method is now compulsory with pubUc 
vaccinators in England. It is also reaUzed that dilution of vaccine Ijonph to 
the greatest degree compatible with activity is a wise precaution. 

Finally every effort must be made to develop a method of protection against 
smallpox without the use of a living virus. 

BIBLIOGRAPHY 

ALDERSHOFF, H.: Recherches sur la cause de rencephalite postvaccinale, Bulletin 

de I'Acad. de Med., Paris, 1930, CHI, 533. 
ARMSTRONG, C: Post vaccination encephalitis, Annals Int. Med., 1931, V, 

BRADFORD, J. R. and BASHFORD, E. F.: Acute infective poljoieuritis, Quart. 

Jour. Med., 1919, XII, 88. 
BROWN, C. L. and SYMMERS, D.: Acute serous encephalitis, Am. Jour. Dis. Child., 

1925, XL VII, 174. 
COLLIER, J. and GREENFIELD, J. G: The encephalitis periaxialis of Schilder, 

Brain, 1924, XL VII, 489. 
DONNELLY, H. H.: Vaccinal encephalomyelitis, Jour. Allerg\% 1931, II, 396. 
FLEXNER, S.: Epidemic (lethargic) encephalitis and allied conditions, Jour. Am. 

Med. Assoc, 1923, LXXXI, 1688. 
FLEXNER, S.: Postvaccinal encephalitis, Trans. Assoc. Am. Phys., 1929, XLIV, 

181. 
FLEXNER, S.: Postvaccinal encephalitis and allied conditions. Jour. Am. Med. 

Assoc, 1930, XCIV, 305. 
Vol. VI. 233 



84(i6) POST-VACCINAL ENCEPHALITIS 

GORDON, A. H.: Post-vaccinal encephalitis, Trans. Assoc. Am. Phys., 1931, XL VI, 

188. 
GRINKER, R. R. and SONTE, T. T.: Acute to.xic encephalitis in childhood. Arch. 

Neurol, and Psychiat., 1928, XX, 244. 
HEKMAN, J.: L'encephalite post vaccinale et son traitement par le serum homologuc, 

Bull, de I'Academie de Med., Paris, 1930, CIII, 539- 
HASSIN, G. B.: A note on the comparative histopathology of acute anterior polio- 

myehtis and epidemic encephahtis. Arch. Neurol, and Psychiat., 1924, XI, 

28. 
HORDER, SIR THOS.: Cerebral symptoms following vaccination, rapid recovery 

after intrathecal injection of post vaccinal serum, Lancet, 1929, I, 

1301. 
MICHELS, N. A. and GLOBUS, J. H.: The so-caUed smaU round-cell infiltrations 

(polioencephalitis and acute epidemic encephahtis). Arch. Path., 1927, IV, 

692. 
MILLER, M. K.: Familiar types of encephahtis, Jour. Am. Med. Assoc, 1931, 

XCVII, 161. 
MUSSER, J. H. and HAUSER, G. H.: Encephalitis as a complication of measles. 

Jour. Am. Med. Assoc, 1928, XC, 1267. 
NETTER, M. A. : Discussion — L'encephalite post vaccinale et son traitement par 

le serum homologue, BuU. de I'Academie de ]\Ied., Paris, 1930, CIII, 

550. 
PERDRAU, J. R.: The histology of postvaccinal encephalitis. Jour. Path, and Bac- 

teriol., 1928, XXXI, 17. 
SHELDON, W. D., DOYLE, J. B. and KERNOHAN, J. W.: Encephalitis periaxia- 
lis diffusa. Arch. Neurol, and Psychiat., 1929, XXI, 1270. 
TURNBULL, H. M. and McINTOSH, J.: Encephalomyehtis following vaccination, 

Brit. Jour. Exper. Path., 1927, VII, 181. 
SCOTT, T. F. McNAIR: Post vaccinal encephahtis, Brit. Jour. Child. Dis., 1930, 

XXVII, 245. 
Ministry of Health of Great Britain: Report upon vaccination, Nov. 1930. 
Editorials: Epidemic constitution, Lancet, 1928, II, 233. The risks of vaccination, 

Lancet, 193 1, I, 85. 
BOYD, WM.: Pathology of Internal Diseases, Lea & Febiger, Phila., 1931. 
McLURE, W. B.: Urticaria and nervous manifestations following vaccination. 

China Med. Jour., 1930, XLIV, 526. 
WRENCH, G. T.: A case of probable post vaccinal encephalitis, Indian Med. Gaz., 

1930, LXV, 443. 
ECKSTEIN, VON A., HERZBERG-KREMMER, H. and HERZBERG, KURT: 

Weitere Beitrage sur Klinik der Vakzinations Enzephalitis, Deutsche med. 

Wochenschrift, 1930, LVI, 1429. 
VON GRUNEBERG: Zur Therapie der Postvaccinalen Encephalitis, Klin. 

Wochenschrift, 1930, IX, 1x27. 
HINRICHS, A.: Enzephalitis nach Vakzination, Centralbl. fiir allg. Path. u. path. 

Anat., 1930, XLIX, i. 
Vol. VI. 233 



BIBLIOGRAPHY 84 (17) 

HENNER, K.: Encephalite apres vaccination antivariolique, Revue Neurologique, 

1930, II, 418. 
BELLI, C. M.: L'Encefalita post vaccinica, Rinascenza Medica, 1930, July i, p. 305. 
ESSER, A.: Die Himschadigungen nach Pochenschutzimpfhung, Virchow's Archiv., 

1930, CCLXXVIII, 200. 
Jan. I, 1933 



Vol. VI. 233 



CHAPTER IV 
BRAIN ABSCESS 

By C. I\1. Hinds Howell 

Table of Contents 

Etiology 86 

Brain Abscess Arising from Some Adjacent Focus of Infec- 
tion 86 
Brain Abscess Arising from Some Remote Focus of Infection 87 

Brain Abscess Arising from Trauma 87 

Unidentified Brain Abscess 88 

Bacteriology 88 

Pathogenesis and Pathology 88 

Paths of Infection from Adjacent Structures ... 88 

Infection bv Direct Extension through the Bone . . 88 

Passage of Infection bv X'^ascular Channels ... 89 

Infection bv Preformed Pathways 89 

Localized Non-suppurative Encephalitis 90 

Otitic Hydrocephalus 90 

Arachnoiditis 91 

Otitic Abscess 9^ 

Metastatic Abscesses 93 

Morbid Anatomy 93 

Cerebrospinal Fluid 94 

Symptomatology 95 

General Symptoms 9^ 

Local Symptoms and Signs 97 

Temporal Lobe Abscess 97 

Cerebellar Abscess 9^ 

Frontal Lobe Abscess 9^ 

Metastatic Brain Abscess 9^ 

Diagnosis 98(1) 

Traumatic Brain Abscess 9^(3) 

Primary Brain Abscess 9^(5) 

Metastatic Brain Abscess _ 9^(6) 

Brain Abscess Due to Extension from a Focus of Infection 9^(6) 

Treatment and Prognosis 9^(7) 

Bibliography 98(7) 

COPYRIGHT 1948 BY THE OXFORD UNIVERSITY PRESS, INC. 

85 



86 BRAIN ABSCESS 

Abscess of the brain Mas recognized during the eighteenth century, 
but it was not until near the end of the nineteenth that the first cases 
of successful treatment by surgery were recorded by iMacE\\'en' in Glas- 
gow, his ^\'ork must be regarded as laying the foundations for the 
present methods of diagnosis and treatment of the condition. 

AMth regard to the general incidence of brain abscess Evans'" found 
that among 14,354 autopsies at the London Hospital (England) from 
1906 to 1925 there were 194 cases. The sex incidence shows a prepon- 
deratino- number in males, althouirh the reason for this is not obvious. 
The age incidence is greatest in the second and third decades, although 
no age group is exempt. 

Etiology 

There are three main sources from which abscess in the brain may 
develop. These are (i) from some adjacent focus of infection, (2) from 
some remote focus of infection and (3) from trauma. Each of these 
must now be considered. 

Bmhi Abscess Arising fro/n Some Adjacent Focus of Infection.— 
The most common source of infection is suppuration in the middle ear 
or labyrinth. Next in order of frequency come infections of the nasal 
or paranasal sinuses. Much less commonly abscess in the brain may 
follow septic conditions of the face, scalp or neck, such as carbuncles, 
ers^sipelas, cellulitis of orbital tissues and so on. Statistics, showing the 
frequency with which suppuration within the cranial cavity has followed 
infection of the ear, have, for the most part, been compiled before the 
advent of the sulfonamide drugs and penicillin. It is almost certain that 
the introduction of treatment with these drugs will reduce very mate- 
riallv the frequency of intracranial complications of infective ear disease. 

However some statistics are worth quoting. Ruegg^ found that 
intracranial complications of ear disease occurred at a Basle clinic 339 
times in connection with 25,203 cases of otorrhoea (1.3 per cent.). 
Turner and Reynolds', quoting records from the Edinburgh Royal In- 
firmary, found 276 intracranial complications in 1 1,826 cases of otorrhea 
(2,3 per cent.). Of the possible intracranial complications of infective 
ear disease abscess in the brain is the least common; among Rucgg's 
339 cases only 28 cases of brain abscess occurred. That infection in the 
ear is a more common cause of brain abscess than nasal infection is 
mtU recognized. Gowcrs, quoted by S.A.K. AA'ilson', found that of 241 
brain abscesses 102 were secondary to disease in the car and a small re- 
VOL. VI, 948 



ETIOLOGY 



87 



mainder to nasal infection. Evans in his series of 194 brain abscesses 
found that 109 followed infection in the ear, and only 12 derived from 
nasal infection. 

Brain Abscess Arising jrovi Some Remote Focus of Infection. — In 
these metastatic abscesses the infection is blood borne. Of these the 
lungs furnish the largest number of cases, bronchiectasis, empyema and 
purulent bronchitis heading the list, whilst abscess of lung, franorrene 
and pneumonia make a smaller contribution. 

The following table compiled from Evans' series sho\\'s the relative 
frequency of the causal factors. 

^es Total 



129 



Method 


Niniiber 


Direct extension. 






Ear 




109 


Nose 




12 - 


Trauma 




8 


Spread by bloodstream. 






From lung (bronchiectasis: 




17 " 


empyema) 




5 - 


Pyaemia 




H . 


Doubtful or unknown. 




17 



46 



17 



In cases of metastatic abscess arising from whatever cause, or in cases 
due to adjacent infection, the abscess may be acute or chronic. Where- 
as in cases due to ear or nasal infection there is almost invariably a single 
abscess, in the metastatic cases, as might be anticipated, either single or 
multiple abscesses may occur. Schorstein*' recorded 1 8 cases of metastatic 
abscess; of these 1 1 were single and 7 multiple. Four only of these had a 
recognizable capsule suggesting some degree of chronicity; the remain- 
ing 14 were all acute. Among 33 additional cases, making 51 in all, 32 
were single and 1 9 multiple. In Evans' series of 1 7 cases 1 1 were solitary. 
It is probably true to say that at least 50 per cent, of metastatic abscesses 
are single, and that the majority of them are acute. 

Blood-borne infection appears to be carried by the middle cerebral 
artery in the majority of cases, the abscess developing more often in the 
centrum ovale than in any other area. 

Brain Abscess Arising from Trauma.— T\\q, frequency with which 
such cases occur appears to be diminishing, apart from war injuries to 
the skull. In Gower's series, quoted by Wilson, among 241 cases no less 
than 24 per cent, were regarded as traumatic in origin, whilst in Evans' 

Vol. VI, 948 



88 BRAIN ABSCESS 

series of 194 cases only 8 were so regarded. Simple fracture of the 
skull, unless it involves an air sinus, is most unlikely to be followed by 
abscess fomiation. and contusion of the brain never, so far as I can dis- 
cover, has caused a brain abscess. Compound fractures, particularly 
those with indriven fragments of bone or metal, are dangerously likely 
to cause the development of an abscess, usually within a short space of 
time, but on occasion either months or even years after the injur^^ 

Unidentified Brain Abscess. — Readers will have noted that in Evans' 
series of 194 cases there occur 17 cases, nearly 9 per cent., described as 
of doubtful or unknown origin. Although it is probably true to say that 
primary brain abscess does not occur, the actual infection of parts either 
adjacent or remote may have appeared quite trivial at the time and their 
incidence have o-one unrecorded. I have met instances of this in connec- 
tion with otitic abscess, M'hen, after the event, a history of preceding 
earache has been recalled, perhaps some months earlier, and in which 
almost certainly the ear was the focus from which the abscess derived, 
another example, were one needed, of the supreme importance of the 
necessity for most minute and thorough anamnesis in all cases. 

Bacteriology.— T\\Q common pyogenic organisms are those most 
often found in cerebral abscess, particularly streptococci and pneumo- 
cocci, although staphylococci are by no means rare, particularly in 
children. Nor rarely the pus in a chronic abscess may be found sterile 
on culture. Among more unusual types B. influenzae, pneumobacillus, B. 
pyocyanens, B. typhosus and the gonococcus must be mentioned. I 
had under my own care a case in which an actinomycotic abscess was 
found in each occipital lobe. 



Pathogenesis and Pathology 
PatJ?s of Infection from Adjacent Structures 

Atkinson" points out that there are three ways in which infection 
may reach the brain, (i) by direct extension through the bone, (2) by 
vascular channels and (3) by preformed pathways. 

Infection by Direct Extension Through the Bone.— By direct cxten- 
tion from the bone the dura is reached and becomes involved in the 
inflammatory process. In many cases, particularly M'hen the infecting^ 
agent is not virulent, the dura forms a barrier to its further progfress. 
Tt becomes adherent around the edge of the inflammatory area, and so 

Vol.. VI, 948 



PATHOGENESIS AND PATHOLOGY 89 

a circumscribed extradural abscess may arise. This seems to occur par- 
ticularly in young subjects and is by no means an uncommon event. Of 
75 cases of intracranial abscess examined at St. Barthlomew's Hospital 
(England) 43 were extradural, and of these 26 occurred in the first 2 
decades of life. If the infection is a highly virulent one, necrosis of the 
dura ensues, and leptomeningitis will occur with or without the forma- 
tion of an acute brain abscess. In less acute infections the meninges 
become adherent to the bone and to the surface of the brain, the general 
subarachnoid space is shut off by adhesions, and a subacute or chronic 
brain abscess may result. 

Ptissage of Injection by Vasndar Channels.— {nitcXAon may reach the 
brain substance and cause abscess formation beneath the cortex either 
bv passage along the perivascular space (\^irchow-Robin), by retro- 
grade thrombophlebitis or by arterial thrombosis and septic infarction. 
Of these alternative paths infection by the perivascular route appears 
much the most common. In Atkinson's series he was able to trace 81 per 
cent, to this path, whilst he found infection by thrombophlebitis twice 
onlv in his 16 cases, and in only one case had arterial infarction occurred. 
It is perhaps prudent to bear in mind that the difficulties at operation or 
post-mortem of being certain of the method of infection are considerable. 

h?fectio7J by Frejorined Pathivays.—Th^st are potential sources of 
infection from disease of the ear. Three such pathways open on the 
posterior surface of the petrous bone into the posterior fossa. These 
are (i) internal auditory meatus, (2) aqueduct of vestibule and (3) 
hiatus subarcuatus. Also in close proximity to the petrous bone lies the 
anterior end of the lateral sinus. Infection travelling by any of these 
routes may cause lateral sinus thrombosis, extradural abscess, meningitis 
or cerebellar abscess, although infection via the internal auditory meatus 
is more likely to cause meningitis than abscess formation. As one or more 
of these conditions may occur in addition to abscess formation in the 
cerebellum, the difficulties of accurate diagnosis need no emphasizing. 

It is important, whilst considering possible ways in which infection 
of adjacent structures may cause abscess in the brain, to mention other 
conditions, to which such inflammation may give rise, as these will of 
necessity come under review when discussing the diagnosis of brain 
abscess. Mention has been made already of lateral sinus thrombosis, 
extradural abscess and leptomeningitis. There are three other conditions 
which must now be referred to briefly; (i) localized non-suppurative 
encephilitis, (2) otitic hydrocephalus and (3) arachnoiditis. 

Vol. Y\, 948 



90 BRAIN ABSCESS 

Localized Non-sup pur Litre e Encephalitis 

This has been described by a number of observers (iVtkinson^, 
Symonds^ Adson", Borries^"). This condition is really indistinguishable 
from abscess clinically. It has been found usually in the temporal lobe 
secondary to ear infection. At operation a softened, inflammatory area 
of cerebral tissue has been found, but there has been no pus formation. 
The prognosis in such cases appears to be better than is the case with 
abscess. 

Otitic Hydrocepbiilus 

This name was suggested by Symonds in 193 i, when he reviewed the 
literature of the subject and added a description of 6 cases which he had 
obser\'ed personally. The condition seems to have been mentioned first 
by Taylor in 1890" in the first edition of his textbook, the Practice of 
Medicine. Quincke^- described cases of increased intracranial pressure 
with clear cerebrospinal fluid which he included in his category of 
serous meningitis. He attributed the condition to otitis media, head in- 
jury, over^^•ork, influenza and alcoholism. \\'arrington^^ described 
conditions of intracranial serous effusions of inflammatory origin and 
noted that there might be an associated hemiparesis. Passot" described 
a similar condition, observed that the incidence was higher in children 
than in adults and found it usually associated with otitis media. It may 
occur without other intracranial complications, but there may co-exist 
for example extradural abscess or lateral sinus thrombosis. The out- 
standincT features of the condition are siras of increased intracranial 
pressure as shown by the presence of papilloedema, often of very high 
degree, recurrent headaches and vomiting, occurring in association with 
aural infections. In the frequent absence of other intracranial complica- 
tions the patient is afebrile. There may be a sixth nerv^e paresis on one or 
both sides or even a hemiparesis. A\'hen free from headache, the patient 
is bright, cheerful and mentally alert in marked contrast to the picture 
presented by a patient with a brain abscess. The cerebrospinal fluid is 
under ver^^ great pressure, frequently overflowing from the top of the 
manometer and on examination is found to be quite normal. Treatment 
is best carried out by repeated lumbar puncture, but it may take weeks 
or months for the condition to subside. Usually there arc no sequelae, 
but optic atrophy may follow occasionally. Symonds thought the cause 
of the condition uncertain. It Mas, he thought, due to either an increased 
Vol. M, 948 



PATHOGENESIS AND PATHOLOGY 91 

production or diminished absorption of cerebrospinal fluid. As there was 
clearly an excess of fluid, he suggested the name of otitic hydrocephalus, 
which seems in my opinion a very adequate description. 



Arncbvoiditis 

Arachnoiditis,^^ inflammation of the arachniod causing thickening 
and adhesions, often associated with cystic collection of cerebrospinal 
fluid, is sometimes found in the posterior fossa and may simulate abscess 
formation. This condition has been described also under the title of 
circumscribed serous meningitis. Chronic infection in the ear and 
petrous bone is the usual cause of this condition, but it also occurs in 
connection with acute infections. 



Otitic Abscess 

Otitic abscess may occur bv \\hatever pathway arising either in the 
tempero-sphenoidal lobe or in the cerebellum, and more often in the 
former than in the latter. The following table gives examples: — 

Number of 

Author Cases Teuiporal Cerebellar Elseivhere 

Oppenheim 76 §^ 13 8 

St. Bartholomew's 

Hospital, London 48 26 22 — 

Evans 109 62 40 7 

Atkinson 21 12 9 — 

The path of infection in cases of abscess in the tevrporal lobe usually 
is via the tegmen tympani or roof of the attic, w^iilst infection of the 
labyrinth and lateral sinus usually leads to cerebellar location. The 
middle third of the temporal lobe is the usual area involved, whilst the 
anterior and outer part of the lateral cerebellar hemisphere commonly is 
involved in subtentorial abscess formation. The abscess is almost in- 
variably on the side of the affected ear, but cases have been recorded 
in which a contralateral abscess has occurred. In such a case the infec- 
tion must have been carried by the blood stream. Brain abscess may be 
acute or chronic, the determining factors being no doubt time and the 
virulence of the infecting organism. The abscess may be entirely sub- 

VOL. VI, 948 



92 BRAIN ABSCESS 

cortical, but frequently pus is found immediately below the cortex or 
quite superficially. The site of the abscess is likely to have an important 
effect on the condition of the cerebrospinal fluid, as in the more deeply 
situated type there may be little or no meningeal reaction, unless there 




Fig. I. — Case of acute brain abscess, opened by opera- 
tion. The abscess has ruptured into the anterior horn of 
the right lateral ventricle. Note softening of cerebral 
tissue in neighborhood of abscess, with hemorrhages, and 
lateral ventricles filled with blood and pus. 

is a co-existing leptomeningitis. In cases of chronic abscess there may 
be a thick fibrous capsule. This in long standing cases may actually 
show evidence of calcification. In the acute variety no capsule can be 
identified, the area surrounding the pus being more or less diffluent with 
punctate hemorrhages and thromboses of small vessels. 

Infection from the iiose^ commonly from the frontal sinus, acts in a 
similar manner to infection from the ear and may cause an extradural 
abscess, leptomeningitis or an abscess in the frontal lobe. In this case 
too the abscess is likely to be single, acute or chronic. 

\'oi.. VT. 948 



PATIIOGFXFSIS AND PATHOLOGY 93 

Metastatic Abscesses 

Metastatic abscesses almost invariably are acute. A good account 
of these has been given by Joseph E. J. King^^ Like other acute brain 
abscesses they are found to consist of a central purulent core, surrounded 
by a zone of necrotic tissue, outside which is a ring of encephalitis. The 
crreat danger in such cases, which is not as a rule long delayed, is 
intraventricular rupture. 

Morbid Anatoviy 

The appearances presented by a brain abscess on examination after 
death depend on the chronicity or otherwise of the abscess. In the acute 
cases there is no definite wall to the abscess cavity, simply a ragged 
margin formed by more or less completely softened and edematous 
cerebral tissue. In these circumstances the contents of the abscess are 
apt to consist of a thin, pinkish material, formed as the result of breaking 
down cerebral tissue, with the addition of a certain amount of blood 
and pus (Fig. i). 

In the more chronic cases there may be, and usually is, a very definite 
wall to the abscess cavity, the thickness of which varies with the chron- 
icity of the abscess (Fig. 2 ) . This wall is formed of loose fibrous tissue, 
in connection with which there is a cellular infiltration, in which num- 
bers of plasma cells are usually to be noted. 

The contents of the abscess cavity often are very characteristic, 
greenish yellow, or actually green in color, and often very offensive. In 
a number of chronic cases the pus on culture has proved sterile. There 
is often an extradural collection of pus in abscess formation secondary'' 
to suppuration in connection with the ear or cranial sinuses, though it is 
to be noted that such a collection of pus may exist alone, without the 
occurrence of any cerebral infection. 

In the event of an abscess being unrelieved by operation, its eventual 
termination is by rupture, either internally into the lateral ventricle, or 
externally on tlie surface of the brain. In both cases septic meningitis 
results and death speedily follows. \trv occasionally a cerebral abscess 
may dischartje its contents through the ear, a purulent otorrhea being set 
up. If for any reason the escape of pus becomes restricted, cerebral 
symptoms quickly follow, owing to the increase in the intracranial pres- 
sure that immediately follows. 

Vol. y\, 948 



94 



BRAIN ABSCESS 



Cerebrospinal Fluid 

This should of course form part of the routine neurological exami- 
nation of the patient, but the results of the examination of the fluid are 
very variable. The possible significance of the findings must be \\eighed 
very carefully with the clinical evidence. The findings are complicated 
by the presence or absence of frank leptomeningitis. 

Usually, but by no means con- 
stantly, pressure of the fluid is 
raised. Of 1 2 cases personally ob- 
served the pressure was not raised 
above 120 mm. in 5, was between 
150 mm. and 200 mm. in 5 and 
was between 200 mm. and 300 
mm. in 2. A manometer usually 
is available for measuring the 
pressure accurately, but in its ab- 
sence two drops per second rep- 
resents a pressure of about 150 
mm. 

In 24 cases of proved abscess 
the fluid was clear in 15, turbid 
or cloudy in 7 and purluent in 2. 
Estimated in 22 cases spinal 
fluid protein was stated to be nor- 
mal (20 to 40 mgm.) in 3 cases, 
40 to 70 mgm. in 6 cases, 70 to 
TOO mgm. in 5 cases and over 100 
mgm. in 8 cases, from which fig- 
ures it is clear that some rise is 
the rule, and that this may be 
considerable. 

Usually the cellular contents 
shows some increase numerically, 
but there ma\- be none. The number of cells may vary in cases of uncom- 
plicated abscess. Quite high cell counts may occur without definite 
leptomeningitis being present, and in such cases the fluid is likely to 
prove sterile on culture and the cells to diminish in number with 
repeated lumbar puncture, an event to which Borries has applied the 
term "paradoxical benignancy". In 21 cases of proved abscess the 

\^OL. \l 948 




Fif;. 2.— Case of chronic abscess of hrain 
ill Icin|K)ros|iheiioi(l;il lobe. Note thick 
wall of abscess and absence of inflammatory 
read ion in sinronnding cerebral tissue. 



SYMPTOMATOLOGY 95 

following cell counts were found; 3 cases 5 to 20 cells per cu. mm., 
3 cases 50 to 100 cells, 2 cases 100 to 200 cells, 4 cases 200 to 500 cells, 
2 cases 500 to 750 cells, i case 750 to 1,000 cells. In some of the higher 
counts there w^as evidence of acute leptomeningitis. 

With a deep seated abscess uncomplicated by meningitis there may 
be no increase in cells or protein in the fluid. When the abscess is 
situated nearer the cortex, there is likely to be either a lymphocytic or 
polymorphonuclear reaction in the meninges, whilst with frank menin- 
gitis the cells will be polymorphonuclear. In the series of cases referred 
to polymorphonuclears were present in 19 of the 22 cases and in excess 
in 9 cases. Lymphocytes were in excess in 1 1 cases, and in i case there 
were equal numbers of each. 

The chlorides in the fluid tend to fall with the development of 
leptomeningitis, so the estimation of the chloride content of the fluid 
may be very helpful in diagnosis. A definite fall below 700 mgm. per 
100 c.c. of spinal fluid wdth an increased quantity of protein and a high 
cell count is very suggestive of meningitis. The lower the chloride 
count, the more suggestive it becomes. I have records of a case in which 
a temporal abscess existed in which there were 1,000 cells per cu. mm. 
in the fluid with a chloride content of 730 mgm. per 100 c.c. Culture 
of the fluid was sterile, and there was no generalized meningitis. 

The glucose cojiteijt of the fluid is unaltered with uncomplicated 
abscess, and definite reduction in quantity only occurs in the presence 
of meningitis. 



Symptomatology 

The early symptoms of brain abscess are those of the condition 
which gives rise to it. Acute or chronic infection of the ear or nose, 
suppurative conditions in the lungs, septicaemia or pyaemia, these will 
give rise to fever, tachycardia, anorexia and headache as general symp- 
toms, if the condition is acute, or there may exist chronic otorrhoea or 
a chronic infection of frontal sinus or lung, which will cause their own 
appropriate symptoms. When to these are added signs of increasing 
intracranial pressure, anxiety as to the possibility of intracranial com- 
plications will of course arise. Symptoms in cases of uncomplicated 
brain abscess are general and local. 

Vol. VI. 948 



96 



BRAIN ABSCESS 



Geijej-iil Syviptovis 

For a time there may be a latent period particularly in otitic cases 
durincf which there is little noticeable change in the patient. As the 
abscess develops, there is likely to be an obvious change in personality. 
The patient may become irritable and mentally retarded. Lack of 
attention is combined with listlessness or apathy. Questions will be 
answered possibly correctly after a more or less prolonged latent period. 
I leadache is likely to be a prominent symptom, often a continuous dull 
ache with paroxysms of violent pain. This may be experienced on the 
affected side, and there may be tenderness on 
percussing the bone in the area complained of. 
The tonffue becomes dry and coated and the 
breath offensive. \'^omiting- is likely to occur. The 
bowels are constipated. The temperature chart 
varies considerably, even in uncomplicated brain 
abscess; irregular pyrexia or a normal or subnor- 
mal temperature with occasional peaks of slight 
pyrexia all occur. Never, if one is justified in 
using such a term in medicine, is the temperature 
continuously high. Of course acute cases of ear 
or nasal infection, acute pulmonary conditions and 
so on will cause fever, as will also other intra- 
cranial complications, if these be present, such as 
meningistis or lateral sinus thrombosis. Rigors 
probably will occur with the latter. 

Should an abscess rupture into the lateral ven- 
tricle, there is likely to be an abrupt rise in tem- 
perature and pulse rate as illustrated in the accom- 
panying chart (Fig. 3). In such a case pure pus 
will be found in cerebrospinal fluid. Rupture, 
however, may occur without such dramatic rise in temperature. 

The pulse rate in uncomplicated cases seldom is accelerated and 
may indeed be definitely slowed. With rapidly rising intracranial pres- 
sure this slowing may be very marked, although perhaps not continu- 
ously. Unless frequent observations are made, every hour or half hour, 
the fall in pulse rate to 50 or even 40 per minute may escape observation. 
In the late stages of brain abscess M'ith greatly increased intracranial 
pressure the respiratory rhythm usually changes with the development 
of the Cheyne-Stokes type. If unrelieved, the patient may die from 
Vol. VI.' 948 



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Fig. 3.—H.A.G., aet. 
4$. InHucnza 14 days 
before admission. 
Right sided subcortical 
abscess, which rup- 
tured into lateral ven- 
tricle. Note sudden 
rise in temperature and 
frequency of pulse. 



SYMPTOMATOLOGY 97 

respiratory failure, such an occurrence being more common in abscess 
below the tentorium than elsewhere. Papilloedema is met with less 
commonly than in tumours of the brain, and as with the latter, at first 
may be unilateral. This as in tumour cases may be suggestive as to the 
side on which the abscess is located but is by no means invariably 
homolateral. Short of papilloedema, the retinal veins may be obviously 
congested with slight blurring of the disc margins. 

Examination of the blood rarely is characteristic, although there is 
usually a slight increase in white cells from 10,000 to 12,000 per cu. 
mm., the differential count showing an increase in polymorphonuclear 
cells. 

Local Symptoms iwd Signs 

Local signs and symptoms will depend on the situation of the 
abscess, frontal lobe in cases of nasal infection, temporal or cerebellar 
in otitic cases, usually centrum ovale in cases of metastatic abscess and 
anywhere in traumatic cases. The signs of a local space-occupying 
lesion are identical with those caused by a brain tumour, but as with 
the latter there may be for a long time no definite symptom or sig^n of 
localising value. Under such circumstances the general signs and symp- 
toms are, therefore, the most important indications for further investi- 
gation in the form of exploratory operation. 

I do not propose here to give a detailed description of the symptoms 
and signs which may occur as the result of local disease in different 
areas of the brain. The reader is referred for a description of these to 
the appropriate chapters in this system. I think, however, it is Morth 
referring briefly to the symptoms which I have found the most helpful 
in localisation. 

Teviporal Lobe /^^yre^;'.— Aphasia occurs when the abscess is left 
sided in a right handed individual or is right sided in a left handed 
individual. The type of aphasia in such cases is very characteristic. It 
is known as nominal aphasia, the patient being unable to find the cor- 
rect word for an object, which he can recognize perfectly well, and 
the use of which he can indicate by pantomime. He will recoonize the 
name correctly when it is given him. AA'hen this symptom is only 
present in an early stage, it may be necessary to carrv^ out an extensive 
investigation before evidence of some degree of nominal aphasia is 
found, but it is, in my opinion, the most common and most important 
sign locating the abscess in the temporal lobe. 

Vol. M. 948 



98 BRAIN ABSCESS 

The next most common sign in such cases is weakness of the face 
on tlie opposite side to tiic abscess. This weakness is of the supranuclear 
type and must not be confused with a possible peripheral type of facial 
weakness on the homolateral side due to involvement of the facial nerve 
in the petrous bone. Weakness or absence of the abdominal reflexes on 
the contralateral side also is important. 

A lesion in the temporal lobe extending inwards is likely to disturb 
the optic radiations and to produce a partial homonymous hemianopia. 
The characteristic visual field under these circumstances is one in which 
there is a quadratic defect, usually^ in the superior quadrant, but in 
cases of abscess, bv the time this sign may have developed, the patient 
is more often than not unable to cooperate sufficiently to make the 
test of any value. 

Cerebellar Abscess.— It is important to note that in a large proportion 
of cases there are no definite cerebellar signs present. Nystagmus, when 
due to a cerebellar lesion, usually shows a coarse movement towards 
the side of the lesion and a fine movement towards the opposite side. 
There are, however, other possible causes, of nystagmus to be found 
in the damaged ear itself, e.g. infection of the labyrinth, so that the 
significance of the symptom has to be weighed very carefully in any 
particular case. The type of nystagmus usually is horizontal and ar- 
rhythmic when present in cases of cerebellar abscess, w^hilst in labyrinth- 
ine infection there is a greater probability of a rotary element in it. 
There are two points, which may help to differentiate between labyrinth- 
ine and cerebellar nystagmus, namely that in the former the movement 
is more likely to have a rotatory element and to be finer, and also that 
the nystagmus may be affected by changing the position of the head. 

Frontal Lobe Abscess.— T\\tvQ may be no evidence of a focal char- 
acter in these cases, and only general symptoms suggesting abscess 
fonnation may occur. The presence of a e^rasp reflex or an absent 
abdominal reflex on the opposite side, if present, will be very suggestive. 
Localized tenderness on percussion of the bone is not of much value 
here, as this will occur in any case with sinus infection. 

Metastatic Brain Abscess.— As these cases are embolic in origin, the 
onset in most, as might be expected, is sudden and acute. Severe pain 
in the head, dizziness and vomiting accompanied by a rise in tempera- 
ture occurring in a patient with chronic pulmonar)^ suppuration or 
pyaemia is only too suggestive of cerebral metastasis; within a day or 
two hemiplcgic symptoms are likely to supervene. The pulse rate at 
first at any rate is likely to be raised. It may or may not fall with the 

Vol. VI. 948 



DIAGNOSIS 98(1) 

progress of the abscess. On the other hand the onset in the chronic 
cases may be quite insidious, although the signs, albeit slowly develop- 
ing, are ultimately those of a space occupying lesion. The situation of 
these metastatic abscesses is most commonly in the centrum ovale. 

Prognosis in these cases is very serious. Untreated the average dura- 
tion of hfe in the acute cases was found by Schorstein to be 10 days 
from the onset of cerebral symptoms. The immediate cause of death 
is often rupture into a lateral ventricle followed by a rapidly fatal 
meningitis. 

In Schorstein's paper^ published in 1909, there had never been any 
recovery recorded in the case of a metastatic brain abscess. Hurst^* in 
1925 recorded a case successfully treated by operation, probably a 
chronic abscess occurring in a patient with an empyema. Joseph King^® 
has published an excellent review of the subject when reporting 6 cases, 
on which he operated with recovery in one acute abscess, and mentions 
Roulland^® in 19 17 as reporting the first recovery of an acute metastatic 
abscess treated by operation. King^" stresses the importance of earlv 
operation in these cases, probably not later than the sixth or seventh 
day, and emphasizes the danger of rupture into the lateral ventricle 
being precipitated by operation. 

It seems certain, I think, that the improved technique in treating 
chronic pulmonary suppuration and the advent of penicillin and the 
sulfonamide group of drugs should reduce the incidence of metastatic 
brain abscess ver>^ materially. 



Diagnosis 

The diagnosis of brain abscess may be comparatively easy or on 
the other hand one of the most difficult problems in medicine. \\'here 
a chronic suppurative otitis media exists and the patient develops the 
symptoms already detailed with localising signs of a focal lesion in 
temporal lobe or cerebellum, the diagnosis is reasonably obvious. Great 
difficulty exists in the acute cases, for in them a variety of intracranial 
complications may occur and either mask or simulate the presence of 
a brain abscess; such complications include meningitis, extradural abscess, 
perisinus abscess, lateral sinus thrombosis, circumscribed serous menin- 
gitis, otitic hydrocephalus, acute nonsuppurative encephalitis, very 
rarely diffuse subdural suppuration and what has been termed Graden- 
ego's syndrome. In addition to this, local disease in the inner ear such 

Vol. VI. 948 



98(2) BRAIN ABSCESS 

as acute labyrinthitis may suggest the presence of a cerebellar lesion. 

With regard to the differential diagnosis of these several conditions 
meningitis is established by examination of the cerebrospinal fluid and 
by pyrexia, nuchal rigidity and so on but may be associated with brain 
abscess. Should symptoms suggestive of the latter persist with improve- 
ment of menine^itis by appropriate therapy, the probability of abscess is 
much enhanced. 

Extradural and perisinus abscess produce no diagnostic points peculiar 
to themselves but are likely to be discovered, when the general condition 
indicates operative treatment, as it will certainly do. Lateral sinus 
thrombosis too, although it may be on occasion without obvious 
symptomatology, usually reveals itself by rigors, sweats, swinging tem- 
perature and rapid pulse, symptoms at marked variance with those of 
brain abscess. Headache and mental hebetude are not prominent, while 
vomiting and papilloedema are most unusual. Acute non-suppurative 
encephalitis and diffuse subdural suppuration are undiagnosable till the 
condition is revealed at operation. 

Circumscribed serous meningitis, as it leads to increased intracranial 
pressure, particularly in the posterior fossa, may simulate a cerebellar 
abscess, but the absence of mental hebetude and the normal or near 
normal condition of the cerebrospinal fluid makes the presence of abscess 
doubtful. No doubt operation will be indicated, when the gush of clear 
fluid on opening the cyst establishes the diagnosis. 

Otitic hydrocephalus with its symptoms of severe headache, papilloe- 
dema and often sixth nerve palsy at first sight may appear deceptive. 
It is clearly differentiated by the mental alertness of the patient, absence 
of pyrexia and by the normal character and greatly increased quantity 
of cerebrospinal fluid. As already pointed out, the fluid may be under 
very great pressure. 

Gradenego's syndrome is the name given to a complication of 
mastoiditis which consists of severe headache on the side of the affected 
ear, with sixth nerve palsy on the same side, the latter probably due to 
a toxic neuritis of the sixth nerve as it crosses the apex of the petrous 
bone, where mastoid air cells extend far down that bone. It is clear 
that in these cases of acute otitis with evidence of intracranial extension 
a firm diagnosis of abscess often cannot be made with precision. How- 
ever, as in most of these cases exploratory operation is indicated, the 
evidence of abscess formation is likely to be forthcoming, a remark 
which applies equally to frontal sinus suppuration. 

Vol. VI. 948. 



DIAGNOSIS 98(3) 

Trmnmtic Br am Abscess 

In many of these the diagnosis is difficult or impossible, and for the 
following reasons; in wounds of the head, of which we have seen so 
many examples in the last few years, septic meningitis frequently com- 
plicates the picture, or the abscess may remain latent until rupture and 
the development of meningitis reveal its presence, or, on the other 
hand, cerebritis with edema, but without the formation of pus, may 
lead to a mistaken diagnosis of abscess. 

If meningitis of the convexity of the brain follows an injury in that 
locality, one may meet with headache, vomiting, fever, combined with 
mental changes, such as dullness and drowsiness, deepening perhaps to 
coma. Should this be accompanied by monoplegia or focal convulsions, 
considerable doubt will exist as to whether an abscess has been formed 
or not. Evidence of meningitis in the cerebrospinal fluid does not ex- 
clude the possibility of an abscess being present; nor should its presence 
contra-indicate operation. 

If such symptoms, as just referred to, develop insidiously a week 
or more after an injury, show a tendency to remission and are accom- 
panied by the development of papilloedema, one can surmise that 
an abscess is developing. Focal epilepsy or paralysis is more in favor 
of abscess formation than meningitis alone, but both may occur as the 
result of cerebritis unassociated with abscess formation, as may also an 
infrequent pulse and comparatively low temperature. As an example of 
such a condition the following case is interesting. 

J.B., aet. 24. A\'ounded in right frontal region. Operation next day; 
excision of wound, small depressed fracture of inner table of skull 
enlarged; dura was thought to be intact. September 3, admitted to a 
London military hospital complaining of severe headache, frontal and 
occipital. Insomnia due to headache; drowsy and irritable; no vomiting. 
Temperature rose to 100° F. as a rule in each twenty-four hours, often 
98° to 99° F. Pulse varied from 48 to 60 per minute, small and of poor 
tension. 

September 6. Wound opened up and B.I.P.P. applied; no improve- 
ment in general condition. 

September 10. Still in same condition, but (i) pulsation in wound 
over forehead has ceased; (2) has choked discs with blurred edges and 
congested veins; (3) no positive signs in examination of nervous system. 
Lumbar puncture was performed and fluid reported normal. 
Vol. IV. 848. 



98(4) BRAIN ABSCESS 

September 14. Operation performed, wound enlarged. Dura found 
thickened and adherent over riglit frontal lobe, hicreased tension present. 
Brain explored by puncture but no pus found. 

September 21. Temperature now normal; pulse rate 60 to 72; very 
irritable and negative in mental attitude, 

October 3. Very well; no headache; normal temperature and pulse. 

In this case the symptoms were clearly due to the presence of a 
brain lesion compatible with abscess, but the sequel showed that none 
was present, cerebral edema due to cerebritis having simulated the 
symptoms of an abscess. 

As an example of a latent brain abscess of traumatic origin which 
was unsuspected, I will briefly refer to the folloM'ing case: 

R.R. wounded August 9th, 19 18; fractured vertex with in-driven 
bone fragments. Operation next day with excision of wound and re- 
moval of fragments. 

Left hemiplegia followed the injury at once. 

Condition on October 29, 19 18 on admission to a London military 
hospital; temperature, pulse, respiration normal. Seven and one-half 
inches from nasion there is a cerebral hernia, partially bridged over by 
skin. Anteroposterior diameter of hernia, two inches. Hernia not raised 
particularly nor very tense. Left hemiplegia and hemianesthesia; optic 
discs negative. 

November 8. Condition improving; hernia getting smaller. 

November 13. Woke screaming with pain in head; then became dull 
and lethargic; no rise in temperature; pulse 112 per minute. Cerebro- 
spinal fluid found thick and turbid, due to streptococcal meningitis. 

Died fourteen days later. Meningitis caused by rupture of brain 
abscess into the ventricle. 

In some cases a considerable period has elapsed between the injury 
and the development of symptoms due to abscess formation. 

In a case under my care at the National Hospital, Queen's Square, 
London, the patient was wounded in September, 19 18 in the left occipital 
region. In May, 19 19 he developed fits of general epileptic character. 
In April, 1920 he complained of severe occipital headaches (eighteen 
months after his original injury); papilloedema developed in both eyes, 
and an abscess was discovered in the left occipital lobe. How long the 
abscess had been present in a latent condition is problematical, but it is 
not unreasonable to suppose that it had existed for some months. 
Vol. IV. 848. 



DIAGNOSIS 98(5) 

Prijnary Brain Abscess 

It is very doubtful if such a condition as primary brain abscess ever 
occurs. It is, however, true enough that cerebral abscesses are found at 
operation or in the post-mortem room, which have been quite unex- 
pected, and for which there is nothing either in the cHnical history or 
physical examination to suggest what might have been the origin of the 
infection. It is a matter of great importance to get a really accurate 
clinical history. A\"hilst this is true for any case of disease, it is particu- 
larly important in connection with cases of intracranial disease. It is 
very easy for the patient to forget an earache, a cold in the head and 
so on, unless his attention is particularly directed to such possibilities, 
and the original occurrence may have been quite trivial and so the more 
easily forgotten; yet in all probability the seeds of intracranial trouble 
were sown during this apparently trivial and forgotten infection. 

In the absence of any obvious cause for abscess formation in the 
brain the possibility that such a condition may exist is likely to be dis- 
carded in favor of the more probable existence of a new growth. Lumbar 
puncture and examination of the cerebrospinal fluid might enable an 
accurate diagnosis to be made. 

The following case illustrates very well several points in connection 
with uncomplicated brain abscess, apparently primary in origin. 

T.N., aet. 42, came under observation on Alay 29, 19 18, giving the 
following history. 

Since January a change had been noted in his disposition. He had 
become irritable, depressed and absent-minded. There was no history 
of any preceding illness. In March his eyesight began to fail. On May 10 
he had complained of frontal headache and had an attack of dyspnea. 
May 1 1 he complained of weakness in the legs, more particularly the 
left leg. May 15 he vomited twice and since then had suffered from 
constant frontal headaches. For the week before his admission he had 
not spontaneously taken any food and had had to be fed. He had been 
confused mentally, did not know the days of the week, and so on. 

On examination his memory was found to be defective and his 
powers of attention and cerebration generally below normal. The sense 
of smell was impaired on the right side. There was papilloedema in the 
right eye, but not in the left. He was incontinent; his gait was unsteady; 
the reflexes were natural. 

June 8. Pulse rate had fallen to 64 per minute, he was stuporose; the 
left plantar reflex was now extensor. June 1 1 . Operation. Bone re- 

VOL. IV. 848. 



98(6) BRAIN ABSCESS 

moved over right frontal parietal region; dura tense, not opened. After 
the operation the general condition improved. June i6. Further opera- 
tion. Dura opened. Convolution found flattened; no meningitis. The 
cortex was incised and pus evacuated. The patient went downhill after 
the operation and died. 

Post-mortem: an abscess cavity was found in the posterior part of 
the right frontal lobe, with a fairly definite wall of fibrous tissue. No 
septic focus was found in connection with any of the cranial sinuses, 
nor in the ears. The viscera crenerally were free from disease. 

The history^ and clinical features presented in this case had suggested 
the pressure of a tumor of the brain, and abscess was not suspected. 

The \\'assermann reaction in blood and cerebrospinal fluid was nega- 
tive. Unfortunately there is no record of chemical or cytological exami- 
nation of the fluid. 



Metastatic Brain Abscess 

When a patient, who is suffering from bronchiectasis, lung abscess 
or pyaemia from whatever cause arising, develops symptoms pointing to 
an intracranial complication, the diagnosis, as a rule, will lie between 
meningitis or brain abscess. Lumbar puncture and examination of the 
cerebrospinal fluid ^^'ill quickly differentiate between these conditions. 
It is tme that meningitis may follow the development of a brain abscess, 
but before it does so, the presence of the latter usually will have been 
indicated by the occurrence of severe headaches, drowsiness with in- 
creasing apathy, vomiting and the other symptoms to which reference 
has already been made. 



Brain Abscess due to Extension ]rovi a Focus 
of Infection in the Skull 

The chief sources of such extension, as has been mentioned already, 
are the frontal, ethmoid or sphenoidal sinuses and otitic infection. Spread 
of infection from the frontal or ethmoidal sinuses is more likely to cause 
a brain abscess than a similar occurrence in connection with the sphe- 
noidal sinus, in which case meningitis or cavernous sinus thrombosis is 
the more probable result. There may be no localising signs whatever 
in a case of frontal lobe abscess, and the diagnosis must be made from 

Vol.. TV 848. 



BIBLIOGRAPHY 98(7) 

general symptoms, combined with a careful examination of the posterior 
w all of the frontal sinus at operation. Should the patient's condition not 
improve following operation on the sinus, the brain should be explored 
by puncture. Thickening of the dura behind the sinus is a very sugges- 
tive indication of the brain abscess. 



Treatment axd Progxosis 

As is so often the case, prevention is better than cure. \Mth the 
recent developments in the treatment of infections by penicillin and 
the sulfonamide group of drugs and the advances made by surgery in 
dealing with chronic pulmonary sepsis there are good grounds for 
belief that the incidence of brain abscess will be reduced. 

The improvement in the technique of brain surgery holds out 
prospects of more favourable results when a brain abscess has developed. 
King has shown that even in metastatic abscess, once invariably fatal, 
some success has been obtained. At present the results of surgery have 
never reached MacEwen's figures published towards the end of last 
century in which he was able to record 18 cures in 19 cases. The 
explanation for his remarkable success is no doubt that all his operations 
were done on carefully selected and chronic cases, where a definite 
capsule had formed, but the possibility of success in acute cases pre- 
cludes such waiting tactics at the present time. 



BIBLIOGRAPHY 

1. Al\cEWEN, WAL: Pyogenic Infective Disease of Brain and Spinal 

Cord, Macmillan, New York, 1893. 

2. EVANS, W.: The pathology and aetiology of brain abscess. Lancet, 

193 1, I, 1 23 1 and 1289. 

3. RUEGG, C: Beitrag zur Frage iiber Haufigkeit und A'orkommen 

otitscher Hirnkomplikationen, Inaugural Dissertation. 38 pp., Basel, 
1927. 

4. TURNER, A. L. and REYNOLDS, F. E.: Intracranial Pyogenic Dis- 

eases, Oliver and Boyd, Edinburgh, 193 1. 

5. WILSON, S. A. K.: Neurology, edited by x\. N. Bruce, Arnold, Lon- 

don, 1940. 

6. SHORSTEIN, G. I.: Lecture on abscess of the brain in association 

with pulmonary disease, Lancet, 1909, II, 843. 
Vol. IV. 848. 



98(8) BRAIN ABSCESS 

7. ATKINSON, E. M.: Abscess of the Brain; its Pathology, Diagnosis and 

Treatment, Medical Publications, Ltd., London, 1934. 

8. SYAIONDS, C. P.: Some points in the diagnosis and localization of 

cerebral abscess. Proceed. Roval Soc. Med., 1927, XX, Pr. Ill, 1 1 39; 
Some points in the diagnosis and localization of brain abscess. Jour. 
Laryngol. and Otology, 1927, XLII, 440; Otitic hydrocephalus, 
Brain, 193 1, LIV, 55. 

9. ADSON, A. W.: Pseudo brain abscess, Surg. Clinic, North America, 

1924, IV, 503. 

10. BORRIES, G. V. TH.: L'Encephalite otogene hemorragique. Rev. de 

Lar\ngol., Otol. et Rhinol., 1932, LIII, 49. 

11. TAYLOR, F.: Manual of the Practice of Medicine, ist ed., p. 262, 

Churchill, London, 1890. 

12. QUINCKE, H.: Ueber Meningitis serosa und verwandte Zustande, 

Deutsch. Zeitschr. f. Nervenheilk., 1897, IX, 149. 

13. WARRINGTON, W. B.: Intracranial serous effusions of inflammatory 

origin, meningitis or ependymitis serosa-meningism— with a note 
on "peudo-tumours" of the brain. Quart. Jour. Aled., 19 14, VII, 93. 

14. PASSOT, R.: Meningites et etats meninges aseptiques d'origine otique, 

These de Paris, 99 pp., G. Steinheil, Paris, 191 3. 

15. HINDS-HOWELL, C. M.: Arachnoiditis (president's address). 

Proceed. Royal Soc. A4ed., 1936, XXX (Sect. Neurol.), 33. 

16. KING, J.E.J. : Acute metastatic brain abscess. Southern Surgeon, 1936, 

V, 407. 

17. EAGLETON, W. P.: Brain Abscess, Macmillan, New York, 1922. 

18. HURST, A. F.: A case of cerebral abscess complicating empyema: 

operation and recovery. Lancet, 1925, I, 605. 

19. ROULLAND, H.: Abces metastatique du cervcau au cours d'une 

suppuration pleurale. Trepanation, drainage de I'abces, guerison, 
Paris Chir., 1917, IX, 613. 
September i, 1948. 



Vol. VI. 948 



CHAPTER V 
CRANIO-CEREBRAL INJURIES 

By DONALD MUNRO 

Table of Contents 

Introduction loi 

Physio-Pathology of Cranio-Cerebral Injuries 102 

Cerebrospinal Fluid 102 

Anatomy 102 

Circulation 103 

Pressure 103 

Cerebral Circulation 104 

Arterial 104 

Capillary Circulation 105 

The Perivascular and Pericellular Spaces and Fluid .... 105 

Venous Circulation 106 

The Fundamental Pathology 107 

The Vaso- vagal Reflex 107 

Direct and Contre-coup Damage no 

The History and the Examination no 

History in 

Examination 113 

Roentgenology 115 

The Localization of the Point of Maximum Brain Injury . 119 

General Principles of Treatment 120 

Nursing 120 

Noise, Light, Heat and Cold 120 

Position of Patient 121 

Restraints 122 

Care of the Skin, Mouth, Lips, Teeth and Hair 123 

Food and Fluids 124 

Care of the L^rinary Bladder 125 

Care of the Large Bowel 126 

Care of the Eyes 126 

Care of the Ears 126 

Care of the Nose 127 

Complications Arising Out of Various Cranial Nerve Palsies . . . 128 

Drug Treatment 129 

Methods of Treatment 131 

Non-operative Methods of Treatment 131 

Lumbar Puncture 131 

COPYRIGHT 1939 BY THE OXFORD UNIVERSITY PRESS, NEW YORK, PIC. 

99 



loo CRANIO-CEREBRAL INJURIES 

The Interpretation of Lumbar Puncture Findings 132 

Therapeutic Dehydration 132 

By Mouth 133 

By Rectum 133 

By Vein 133 

Intramuscular 135 

Blood Transfusion 135 

Operative Methods of Treatment 136 

Non-operable Group of Cranio-Cerebral Injuries 136 

Concussion 136 (i) 

Edema and Congestion 136 (i) 

Contusion and Laceration 136 (3) 

The Operable Group of Cranio-Cerebral Injuries 136 (4) 

Subdural Hemorrhage 136 (5) 

Compound Fractures of the Skull 136 (9) 

Extradural Hemorrhage 136 (11) 

Depressed Fractures of the Skull 136 (14) 

Lacerated Wound, Avulsion and Hematoma of the Scalp .... 136 (15) 

Complications of Cranio-Cerebral Injuries 136 (16) 

Complications Due to Associated General Bodily Conditions . . . 136 (17) 

Surgical Shock 136 (17) 

Toxic Dehydration 136 (18) 

Complications Due to Infection in the Cranium and Cranial Cavity . 136 (19) 

Meningitis 136 (19) 

Brain Abscess 136 (21) 

Osteomyelitis and Infected Scalp Wounds 136 (22) 

Simple and Complicating Fractures of the V'ault and Base of the 

Skull other than Compound or Depressed Fractures . 136 (22) 
Injuries Other Than Those of the Cerebrum, Cerebellum and Men- 
inges that are Associated with Simple Fractures .... 136 (23) 

Traumatic Arterio-venous Aneurysm 136 (24) 

Complicating Fractures of the Skull 136 (25) 

Fractures of the Temporal Bone 136 (25) 

Fractures Involving the Cribiform Plate or Paranasal Sinuses 136 (27) 

Fracture of the Posterior Wall of the Frontal Sinus .... 136 (27) 

Aerocele 136 (28) 

Complications Due to Necessar>' Treatment 136 (28) 

Bilateral Subtemporal Decompression 136 (28) 

Post-operative Defects in the Skull Bones 136 (29) 

Supra-orbital Defects 136 (30) 

Parieto-frontal Defects 136 (30) 

Foreign Bodies in Cranio-Cerebral Wounds 136 (31) 

Broken Lumbar Puncture Needles 136 (32) 

Post-operative Cerebrospinal Fluid Fistulae 136 (32) 

Fungus Cerebri 136 (33) 

Incontinence and Lumbar Puncture 136 (33) 

Cranio-Cerebral Injury in the New-Born 136 (33) 

Fundamental Intracranial Pathology 136 (35) 

Additional Cranial and Intracranial Pathology 136 (35) 

Vol. VI. 339 



INTRODUCTION loi 

Hemorrhagic Disease of the New-Born 136 (37) 

History and Symptomatology 136 (37) 

Signs and Symptoms 136 (39) 

Treatment 136 (39) 

The Xon-operable Intracranial Injuries of the New-Born .... 136 (41) 

Asphyxial Intracranial Injury of the Xew-Born 136 (41) 

The Inoperable Traumatic Cranial and Intracranial Injury in the 

New-Born 136 (42) 

Meningeal Tears, Ruptures of Venous Sinuses, the Vein of Galen 

and the Internal Cerebral Veins 136 (42) 

Non-complicating Fracture of the Skull in the New-Born 136 (43) 

The Operable Cranial and Intracranial Injuries of the New-Born . 136 (43) 

Subdural Hematoma 136 (43) 

Extradural Hematoma 136 (45) 

Depressed Fracture of the Skull 136 (45) 

Complications of Cranial and Intracranial Injuries of New-Born . . 136 (46) 

Surgical Shock 136 (46) 

Toxic Dehydration 136 (47) 

Central Nerv'ous System Infection 136 (47) 

Fetal Meningitis 136 (47) 

Contusions of the Face and Scalp, Cephalhematomas and Caput Succe- 

daneum 136 (47) 

Contusions of the Face and Scalp 136 (48) 

Cephalhematomas 136 (48) 

Caput Succedaneum 136 (48) 

Ratio of Occurrence, Mortality and Morbidity of Intracranial 

Hemorrhage of New-Born 136 (48) 

First Aid in Cranio-Cerebral Injuries 136 (49) 

Convalescent Care of Cranio-Cerebral Injuries 136 (54) 

The First Period of the Convalescence 136 (55) 

The Second Period of the Convalescence 136 (55) 

The Third Period of the Convalescence 136 (57) 

The Chronic Post-traumatic Neurotic 136 (58) 

Bibliography 136 (60) 

Introduction 

Although the treatment of cranio-cerebral injuries belongs, in the last 
analysis, in the field of surgery, the prevalence of these lesions makes it 
imperative that every practising physician be familiar not only with the 
physio-pathology involved but with the diagnosis, the general principles 
of treatment and the maximum permissible morbidity and mortality that 
should accompany each individual type of injury. With this knowledge 
the physician is able to deal competently with the emergencies, he will 
recognize the need for surgical or special consultants at the earliest possi- 
ble moment and will know whether or not the surgery, that is being prac- 
tised on his patient, is proper and in conformity with the pathological 

Vol. VI. 339 



102 CRANIO-CEREBRAL INJURIES 

requirements and of a type that can be expected to give the patient his 
best chances for recovery without morbidity. This does not, and should 
not, in a text-book on medicine imply any discussion of the purely tech- 
nical aspects of any operative procedure. The physician must leave that 
to the surgical consultant, whose knowledge and efficiency are tested by 
the results he obtains and not by carping criticism of meticulous details 
of technical procedure. On that account this section will be devoted 
largely to a discussion of the non-surgical aspects of cranio-cerebral in- 
juries. Other information must be sought for, if desired, from other 
sources, references to which are listed at the end of the section. 



PHYSIO-P.A.THOLOGY OF CrANIO-CEREBRAL INJURIES 

Cerebrospinal Fluid 

Anatomy. — The cerebrospinal fluid in all probability is a dialysate, 
which has been filtered from the blood stream into the ventricular system 
of the brain by the choroid plexus. It leaves the ventricular system 
through the foramen of Magendie in the roof of the 4th ventricle to be 
distributed throughout the cranial and spinal subarachnoid spaces. At 
certain points in relation to the brain stem and the base of the brain the 
subarachnoid space is dilated locally. The dilatations are spoken of as 
cisternae or cisterns and the cerebrospinal fluid "puddles" in them. The 
best known of these cisternae is the cisterna magna, which surrounds the 
junction of the cervical spinal cord with the medulla, and which lies just 
beneath and on either side of the rim of the foramen magnum. It is at 
this site that the cisternal puncture as devised by Ayer is made. It is 
well to emphasize here that this cisternal puncture is never required for 
either the diagnosis or the treatment of any cranio-cerebral injury and, if 
used under such circumstances, is an extremely dangerous procedure. 
Other cisternae are the lateral cerebellar, the pontine, the chiasmal and so 
forth. The rest of the subarachnoid space overlies the cerebral, cerebellar 
and spinal pia with its enclosed vessels and immediately underlies the cra- 
nial and spinal arachnoid. It is broken up by innumerable filmy trabeculae 
and is crossed at intervals by veins, which have originated as branches of 
the pial veins and are on their way to empty into dural veins or into some 
one of the large, dural, venous sinuses. Such vessels usually are referred 
to as bridging veins. From the time they leave their parent pial vein 
until they reach their destination in the dura their walls are entirely with- 
out support and their ability to lengthen without rupture at a minimum. 
The cerebral subarachnoid space is characterized further by the presence 

Vol. VI. 339 



PHYSIO-PATHOLOGY 103 

of arachnoidal villi or Pacchionian bodies. These structures are out- 
pouchings of the arachnoidal membrane into the venous blood stream. 
Thus, the subarachnoid space is not actually in contact with the blood 
stream but is separated from it by the greatly attenuated dural wall of 
the sinus and the arachnoid itself. This intervening wall is perforated by 
many small openings. These are less than the diameter of a red blood 
corpuscle and, therefore, permit the movement of fluid, but not of cells, 
from one side to the other. It is through these structures that the cerebro- 
spinal fluid is absorbed into the cranial venous system. 

Cerebrospinal Fluid Circulation. — The cerebrospinal fluid is being 
constantly produced at all times. It fills the ventricles, the cisternae and 
the spinal, cerebellar and cerebral subarachnoid spaces. To do this, it 
must be manufactured at a positive pressure. Only in this way can these 
various cavities be kept in a state of normal distention. However, to 
prevent over-distention and in view of the constant replenishment of the 
supply provision must be made whereby the excess fluid can be removed 
as constantly as formed. This, as pointed out above, takes place via the 
arachnoidal villi into the cranial venous blood stream and is possible only 
because the normal cerebrospinal fluid pressure is slightly greater than 
the normal intracranial venous pressure. It will be apparent that in such 
a mechanism, the two pressure levels must be interdependent, and altera- 
tions in either one must afifect directly and at once the height of the 
other. Thus, while under normal conditions the flow of cerebrospinal 
fluid will be constantly out of the ventricles into the subarachnoid space 
and thence into the cranial venous system, a wide variety of abnormalities 
may be expected to reduce this movement to any degree and even to stop 
the stream completely. 

Cerebrospinal Fluid Pressure. — The normal cerebrospinal fluid pressure 
has been known for a long time. It varies with the position and size of 
the patient. The standard measurements are those for adults lying com- 
pletely relaxed on either side and with the head level with the pelvis. 
These measurements are commonly made by tapping the lumbar sub- 
arachnoid space. Under these conditions the normal cerebrospinal fluid 
pressure is known to lie between 8 and 10 mm. of mercury and 90 and 
160 mm. of water. Figures slightly above or below these limits may be 
normal in the individual case. The amount of dehydration, the size of 
the individual, the efficiency of his circulatory system and especially the 
degree of relaxation are all factors which may or may not be recognizable 
but which can produce variations from the figures given above. The 
measurements in the new-born have been made only on the mercury scale. 
This normal pressure ranges from 2 to 5 millimeters of mercury. It is not 

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I04 CRANIOCEREBRAL INJURIES 

known when the change to adult levels takes place, nor how gradual it is. 
Measurements, used with the patient in the erect position and at the same 
point, show that in an adult the lumbar pressure will be more than dou- 
bled. The intracranial pressure, on the other hand, will be less than at- 
mospheric and range from minus 50 mm. in the ventricles to 150 mm. in 
the lumbar sac, while the zero point between these two extremes will be 
found to be at about the level of the lower cervical vertebrae. Analogous 
measurements have not been made on the new-born. Changes in cerebro- 
spinal fluid pressure, which for practical purposes is the same thing as 
intracranial pressure, follow any alteration in the volume of any of the 
contents of the skull. This, except in unimportant details, was first stated 
in 1824 as the Monro-Kellie doctrine and predicates that variations in any 
one of the three elements within the cranium, viz. brain, blood or cerebro- 
spinal fluid, may occur, but any alteration in the volume of any one is 
compensated for at once by an alteration in one or both of the others. 
Thus, it will be seen that, if the brain volume is increased, as in edema, 
the amount of cerebrospinal fluid may be reduced and the size of its res- 
ervoir curtailed. So too with an increase in the volume of intracranial 
blood as, for example, in congestion associated with anoxemia, the same 
thing may happen. In either case, the cerebrospinal fluid or intracranial 
pressure rises, inasmuch as the production of the spinal fluid continues in 
the face of the reduction of the reservoir. Conversely, when the brain 
shrinks, as in dehydration, the cerebrospinal fluid reservoir is enlarged, 
and until the extra intracranial space that has been produced in this way 
is again distended by fluid, the intracranial pressure will be below normal. 

Cerebral Circulation 

Arterial. — Arterial blood is brought to the brain by four main arte- 
ries, the two vertebral and the two internal carotid arteries, and is dis- 
tributed evenly from them to all six cerebral trunks. Thus, an adequate 
supply of arterial blood is insured to both hemispheres even if one carotid 
be shut ofT. The branches from the six main trunks divide in such a way 
as to supply the basal ganglia, the choroid plexus and some of the deep 
white matter. Most of them, however, run directly to the surface of the 
cortex where they spread out in the pia. From these vessels arterioles 
perforate the surface of the brain and plunge directly downward into the 
cortex and subcortical white matter. At these levels they branch again 
and again and eventually enter the capillary bed. These arterioles and 
capillaries have a rich anastomosis with branches from other arterial 
trunks including those that have ascended from the vessels that have 

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PHYSIO-PATHOLOGY 105 

come up through the basal gangUa and white matter. There are no end 
arteries in the brain. All of these vessels, however, and especially the 
arterioles, are under the control of the vasomotor apparatus, although to a 
lesser degree than the other parts of the arterial tree. As a result they 
may either dilate or go into spasm as the result of impulses that arise 
outside of the cranial cavity. 

Capillary Circulation. — The capillary network is much more dense in 
the gray than it is in the white matter and also has a rich anastomosis. 
Blood flow in any given capillary loop is directly dependent upon the 
degree of contraction of the arteriole that leads to that loop. Under 
normal conditions the resulting intracapillary pressure at the arterial end 
of the loop is kept constantly at a slightly higher level than the osmotic 
pressure of the tissue fluid which surrounds the loop. These pressures 
being antagonistic, the higher hydrostatic pressure insures movement of 
oxygen-laden nutrient fluid outward into the perivascular and thence into 
the pericellular spaces. At the venous or opposite end of the same loop 
the hydrostatic pressure inside the vessel is less than the colloid osmotic 
pressure. As a result the movement of fluid will be out of the pericellular 
and perivascular spaces across the capillary wall into the lumen of the 
vessel. In this way provision is made for the removal of oxygen-poor 
tissue fluid from about the cells into the venous circulation. It must be 
evident then that any change, such as an increase in the intracapillary 
pressure or a dilution of the blood plasma, will result in the movement of 
more fluid from the arterial side of the loop into the perivascular spaces 
as well as an associated diminution of flow of this same fluid from the 
tissue spaces into the venous end of the loop. So, too, alterations in the 
protein content of the perivascular fluid will alter the relative osmotic 
pressure of the blood plasma and the tissue fluid and will, of itself, alter 
the amount and absorption of the pericellular fluids. 

The Perivascular and Pericellular Spaces and Fluid. — All of the large 
and small arteries and veins contained within nervous tissue are enclosed 
in a well-defined perivascular space. This space is not discernable as such 
about the arterioles, venules and capillaries but is present potentially. 
When it is distended, it can be shown to be continuous with the peri- 
vascular spaces about the larger vessels. In the other direction it has been 
demonstrated that this pericapillary space is continuous with the peri- 
cellular or perineuronal spaces. In conformity with this arrangement it 
has been found that the capillaries are in close approximation to the in- 
dividual nerve cells. Furthermore, they are more numerous in the cellular 
as opposed to the axonal layers of the brain, the ratio being about 5 to i. 
Although it has not proved practical to collect or analyze it, the peri- 

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io6 CRANIO-CEREBRAL INJURIES 

cellular spaces undoubtediy contain extracellular tissue fluid. This fluid 
orio;inates from the blood plasma and passes from the pericellular into the 
pericapillary and perivascular spaces. From this point the flow continues 
toward the surface of the brain, where the fluid empties into the sub- 
arachnoid space. The drainage takes place through a perforation in the 
pia, which is primarily present to admit a blood vessel. It is restricted to 
a minimum because of a ring of inelastic fibrous tissue which surrounds 
the vessel like a collar. This restriction not only prevents excess drainage 
of tissue fluid but also the regurgitation of cerebrospinal fluid from the 
subarachnoid space into the subsurface regions. Pericellular fluid nor- 
mally has a lower concentrate of protein molecules than blood plasma. 
Being separated by a dialyzing membrane, the capillary wall, and being 
subject to the law of osmosis, it will follow that, if otherwise uninfluenced, 
there will be a constant flow of the fluid with the lower molecular con- 
centration toward the fluid with the high molecular concentration. These 
relative osmotic pressures, therefore, tend to move fluid into the capillary 
loop from the tissue spaces. As was noted above, this movement is held 
in check by the antagonistic hydrostatic pressure within the arterial end 
of the capillary loop and facilitated by the lowering of that same pressure 
in the venous end of the loop. An abnormal decrease in the molecular 
concentration or protein content of the plasma or a corresponding increase 
in the same contents of the tissue fluid may so alter the relative osmotic 
pressures as to produce not only an excessive outpouring of the former 
from the arterial end but a diminution of the absorption of the latter into 
the venous end. 

Venous Circulation. — The venous blood after leaving the capillary bed 
passes into the large dural sinuses by way of intervening venules and 
small veins. These vessels are more numerous and have more anasto- 
moses than the arteries. They are roughly divided into two systems. 
One system drains the ventricles, the choroid plexus and the basal ganglia 
and empties into the vein of Galen by way of the internal cerebral veins. 
This blood leaves the skull through the straight and lateral sinuses to 
empty into the jugular bulbs. The other system drains the subcortical 
and cortical tissues into vessels that lie enmeshed in the pia on the surface 
of the hemispheres. These empty into the large dural sinuses, chiefly the 
two lateral and the sagittal, the blood again leaving the skull by way of 
the jugular bulbs. It is from this group of veins that the bridging vein, 
referred to above, arises. Mixed with the venous blood after it reaches 
the sinuses is the excess cerebrospinal fluid, which has escaped from the 
subarachnoid space by way of the arachnoidal villi as described above. 
Cranial venous blood circulates at a positive pressure, which is normally 

Vol. VI. 339 



PHYSIO-PATHOLOGY 107 

slightly less than that of the cerebrospinal fluid. The entire venous sys- 
tem reacts rapidly to any interference with the flow in any part, and the 
intravenous pressure is sufficiently low in the intracortical part of the 
system, at any rate, to olTer little resistance to extraneous compression 
such as that exerted by tissue edema. Congestion quickly develops, and 
it is but a short step from there to stasis and thrombosis or rupture or 
both. It is because of the widespread and often unexpectedly lethal ef- 
fect of congestion on the cerebral cells that compression of the jugulars in 
doing the Queckensted test in the presence of cerebral injury is contra- 
indicated. It adds more congestion to an already over-distended cranial 
venous system and may be reasonably expected to rupture veins that 
might not otherwise break. 

The Fundamental Pathology 

There are certain pathological changes which are constant in all cranio- 
cerebral injuries that have been accompanied by any degree of unconscious- 
ness. They produce alterations in the normal activities of the cerebral 
circulation, the volume of the brain and the absorption of the cerebro- 
spinal fluid. These are demonstrable clinically as changes in the cerebro- 
spinal fluid or intracranial pressure and the presence or absence of blood 
in the subarachnoid space. They constitute the pathology of all the non- 
operable cerebral injuries. It is to this pathology that the changes asso- 
ciated with the operable cranio-cerebral injuries and the complications 
that may be associated with either group are added. An understanding 
of, and familiarity with, this fundamental pathology and the diagnostic 
and therapeutic requirements that arise out of it are indispensable, if one 
would assume the responsibility for the welfare of patients with cranio- 
cerebral injuries. 

The Vaso-vagal Reflex. — When an individual is struck on the head 
sufficiently hard to produce any degree of unconsciousness, a reflex dila- 
tion of the cerebral arterioles is produced. This is the vaso-vagal reflex. 
It may arise as the result of many extra-cerebral stimuli of which pain 
and fright are two important ones. The stimulus travels by way of the 
vagus and vasodilator nerves and affects the heart and the arterial side of 
the circulatory system. It produces sweating, pallor, a lowered blood 
pressure, a cessation or diminution of respirations and a dilatation of the 
arterioles with a resultant rise in the intracapillary hydrostatic pressure. 
This rise follows the throwing open of the capillaries to the large volume 
of circulating blood previously held in check by normal arteriolar con- 
tractility. If the injury has been such, or the patient's circulation is so 

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io8 CRANIOCEREBRAL INJURIES 

efficient that recovery of consciousness takes place before the circulatory 
changes have progressed beyond this point, there will be no further symp- 
tomatology. This will apply not only to the objective demonstration of 
signs but also to the subjective complaint of symptoms. This amount of 
post-traumatic cerebral pathology is self-limited, requires no therapeusis 
and constitutes the syndrome that goes under the diagnosis of concussion. 

If the injury has been more severe or the circulation less efficient, the 
pathological changes will, of necessity, be greater. The period of uncon- 
sciousness, however, need not be affected. The changes instituted by the 
vaso-vagal reflex serve now as the first step of more serious and wide- 
spread pathology. The dilated arterioles and the increased intracapillary 
pressure dilate the capillary loop and raise the hydrostatic pressure 
within it to such levels as to cause an outpouring of plasma from 
the arterial end into the surrounding perivascular and other spaces. These 
same factors lead to a reversal of the ordinary relationships between the 
hydrostatic capillary venous pressure and the relative osmotic pressures 
of the tissue fluids and the venous blood plasma. This prevents the 
absorption by osmosis of the excess tissue fluids into the capillary venous 
stream. The pericapillary tissue spaces distend, venules are compressed 
or collapsed from the pressure of this distention, and the circulation in 
the smaller vessels may be stopped or even reversed. A high degree of 
tissue anoxia follows with swelling and destruction of cells. The brain 
volume increases, the cranial venous pressure rises, and partly as the re- 
sult of a diminution of the size of the reservoir and also as the result of 
diminution of absorption of cerebrospinal fluid from that reservoir into the 
large venous channels because of the relatively higher venous pressure, 
the cerebrospinal fluid or intracranial pressure is raised. Associated with 
the more serious phases of these changes may be thrombosis or rupture of 
intracortical veins with areas of hemorrhage or cell destruction that tend 
to coalesce. As a result, all varieties and degrees of alteration of periph- 
eral function may follow and remain permanently, if the damage has been 
extensive enough. This degree of post-traumatic cerebral pathology may 
be either self-limited or progressive. If the former, the resultant perma- 
nent symptomatology will vary with the amount of cellular destruction, 
but in the latter the process will end by causing the death of the indi- 
vidual. The therapeusis must, of necessity, be directed toward the lower- 
ing of the increased intracranial pressure, the elimination of the venous 
congestion and the reduction of the increase in brain volume. This syn- 
drome goes under the diagnosis of congestion and edema or edema of the 
brain. The term concussion should be added to this diagnosis to make it 
accurate and complete. However, custom has decreed that this be not 

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PHYSIO-PATHOLOGY 109 

done, and, since its omission is of no therapeutic consequence and, there- 
fore, cannot harm the patient, it does not seem worthwhile to insist upon 
its inclusion. 

When the injury is even more severe, it will cause, in addition to the 
concussion and edema and congestion as described above, either a con- 
tusion, or laceration, or both, of the surface of the brain. With either of 
these conditions one or more of the surface blood vessels will be ruptured, 
the pia torn and blood be emptied into the subarachnoid space. Because 
of their thinner and less elastic walls as well as their numerical prepon- 
derance, this bleeding is, to all intents and purposes, from the veins and 
not from the arteries. It is greater in amount and continues for a longer 
time when the veins are congested, the amount and length of time varying 
directly with the amount of congestion. Per contra it stops of itself, ex- 
cept for the dural sinuses, when the congestion and, therefore, the intra- 
venous pressure is lowered to normal. This extravasation of serum, and 
in particular of red blood cells into the cerebrospinal fluid, introduces in 
addition to the edema and congestion a mechanical blockade of the ave- 
nues of escape of the cerebrospinal fluid. 

Thus, the already abnormally high intracranial pressure is raised still 
further by the plugging of the orifices of the arachnoidal villi by these 
free cells. This plugging continues to a varying degree until such time 
as the phagocytic meningocytes shall have disposed of the abnormal 
subarachnoidal cellular contents. In the meantime the cerebrospinal 
fluid is backed up in its reservoir; the cerebral veins and the cerebrum 
itself are subjected to the resulting pressure; the congestion, tissue 
anoxia and edema are increased and the cranial venous pressure raised 
to new heights. A vicious circle is produced which can be broken only 
by the mechanical drainage of the excess backed up cerebrospinal 
fluid. 

It has been said that this therapeutic reduction of the high intra- 
cranial pressure will promote more bleeding, and that, therefore, it is con- 
traindicated. Such a statement has, as can be seen, no basis in fact and 
serves only to betray the ignorance of the author in regard to the funda- 
mental pathology of the injury with which he has had to deal. Such con- 
ditions are commonly spoken of as contusion and /or laceration of the brain. 
In the interests of accuracy and for the purposes of treatment it would 
be much better for the patients if it were universally recognized by the 
medical profession that the diagnosis should include edema and congestion 
in addition. In this way both dehydration and decompression by drain- 
age of cerebrospinal fluid would be assigned their proper places as thera- 
peutic agents in the management of the patient. 

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no CRANIOCEREBRAL INJURIES 

Direct and Contre-coiip Damage 

Much has been made in the past of the importance of contre-coup 
damage to the surface of the brain. Knowledge of its presence is impor- 
tant as a measure of the extent of the surface damage to the cerebrum 
or as a potential site for the source of a subdural hematoma. The im- 
portance of the first fades into relative insignificance from a therapeutic 
point of view when it is considered in relation to the much more wide- 
spread and more damaging subcortical changes. In the latter case little 
practical significance can be attached to the knowledge, since the final 
diagnosis of any subdural hematoma must rest on a bilateral exploratory 
trephination. 

Academically, however, it is known that contre-coup damage to the 
surface of the brain of whatever grade only takes place when the injury 
is caused by the forcible contact of the moving skull against a stationary 
object. The local direct damage occurs on the surface of the cerebrum 
immediately opposite the point of contact. The contre-coup damage is 
located on the surface of the brain at a point corresponding to the op- 
posite extremity of the hypothetical chord which originates at the point 
of impact of the blow and subtends the longest and flattest arc of the 
cranial vault. 

With the skull and its contained brain both in motion in the same 
direction, the brain, because of its relatively greater inertia, lags slightly 
behind the bone. At the moment of impact the apex of the arc in ques- 
tion either bends outward or breaks. This permits its distal extremity 
to move sharply inward against the surface of the lagging cerebrum. The 
amount of damage done to the latter organ will depend upon the amount 
of inertia of the brain, the weakness of the bony arch and the abruptness 
with which the motion is arrested. 

The History and the Examination 

There are certain essential historical and physical data that must be 
obtained in every case of cranio-cerebral injury before the ultimate diag- 
nosis can be made. There are other data which may be obtained, notably 
in connection with such special examinations as the making of x-ray 
films of the skull, the immediate procurance of which popularly is sup- 
posed to be essential, but which is not only useless but subjects the 
patient to undue risk. An understanding of these points is requisite to 
the proper management of the condition, whether the ultimate therapeusis 
is operable or non-operable. 

Vol. VI. 339 



THE HISTORY AND THE EXAMINATION in 



History 

Since generally it is taken for granted that cranio-cerebral injuries 
result from contact between the patient's head and some solid object, the 
most important historical datum that can be obtained has to do with the 
presence or absence of unconsciousness. For practical purposes and be- 
cause the exceptions to the rule are so rare, it may be stated that no 
cerebral injury occurs without some degree of unconsciousness. It is not 
as easy to verify this statement as would appear on the surface, however. 
There is a complete disagreement among the profession and the laity as 
to what constitutes unconsciousness. There is also the ever present desire 
on the part of the patient to color his story, if for no other reason than to 
please the doctor. Furthermore, there will be times when the patient is 
unconscious but does not know it on account of the static quality of his 
surroundings, and other times when observing witnesses fail to recognize 
unconsciousness that the patient is aware of, because his actions appear 
to be normal. Obviously, a definition is essential. This has been made 
available only recently by Cobb. He emphasizes that consciousness is a 
manifestation of the organism while in action. It is made up of many 
elements, must of necessity have many degrees and must be integrated 
at many levels. Thus, one form of consciousness, which we commonly 
recognize, includes the integrated functioning of such basic attributes as 
respiration and the maintenance of circulation with the individual ability 
to read an absorbing book. Such a person will be conscious in one sense, 
but to the man who is being robbed around the corner from him and 
whose cries for aid do not penetrate the concentrated attention of the 
reader, the latter is, to all intents and purposes, unconscious. At the 
other extreme is the individual whose only connection with his surround- 
ings, as far as the observers know, is the maintenance of his circulation 
and respiration. Thus, it can be seen that there is neither ever any state 
which is actually full consciousness nor any condition short of actual 
death when there is full unconsciousness. This concept of consciousness 
and its loss includes all the stages that have been popularized under such 
terms as dizziness, blackness, being dazed, being confused, response or 
lack of response to varying degrees of painful stimuli and so forth. With 
this in mind the doctor will never be content to accept the patient's as- 
sertion that he was either conscious or unconscious after an accident. He 
will put such a statement to the test from the point of view of the im- 
pairment of the patient's contact with his surroundings in all spheres of 
mental as well as physical activity. To do this successfully will require 

Vol. VI. 339 



112 CRANIO-CEREBRAL INJURIES 

a considerable degree of lawyer-like cross-questioning. However, when 
doing this, the physician should studiously avoid any appearance of at- 
tempting to fix the legal responsibility for the damage. This does not 
come properly within his province and attempts to include it as part of 
his medical data will lead him into difficulties all too frequently. It should 
be obvious in this connection that the actual mechanics of the injury are 
of no importance in the treatment of the patient. The acquirement of 
these data lead to a wasting of valuable time. After all a patient dies as 
completely from an undiagnosed and untreated cerebral lesion whether it 
was caused by a fall on a wooden floor or by an automobile accident. 

Having demonstrated a loss of consciousness, it is important to ascer- 
tain next whether or not there was a conscious interval. If it can be 
shown that such an interval was present, it must be considered as pathog- 
nomonic evidence of cerebral extra- or sub-dural hematoma until proved 
otherwise. During the conscious interval the patient normally is in con- 
tact with his surroundings and may be, unless cross-questioned, entirely 
unaware of the fact that unconsciousness preceded this state. An his- 
torical sequence of a blow on the head followed by a period of conscious- 
ness, which in turn is succeeded by a period of advancing coma, should 
be regarded as suspiciously as though a period of unconsciousness immedi- 
ately following the receipt of the blow had been included in the descrip- 
tion. 

The history will prove a useful means of checking on the possible 
presence of such extraneous objective factors as may be expected to lead 
to complications of the cerebral injury. Chief among these are toxic de- 
hydration and exhaustion. Vomiting and exposure to heat, whether from 
the sun or from injudiciously applied coverings, and especially if combined 
with intended or accidental limitation of the fluid intake lead to the first. 
Exposure to cold, long journeys and associated major injuries lead to the 
latter. 

When taking the patient's history at any appreciable interval after 
the injury, the facts as given should be scrutinized with more than usual 
care. Intentional and unintentional misstatements abound. Financial and 
legal complications have arisen, the attitude has become emotional rather 
than rational, and it may prove impossible to get data in regard to the 
presence of unconsciousness that is reliable. In such circumstances the 
doctor may find it helpful to determine whether or not the patient had a 
headache after the accident and, if so, for how long and to what extent. 
Such a symptom developing shortly after the accident and lasting steadily 
for a few hours up to a number of days is an almost invariable accom- 
paniment of any cerebral injury greater than concussion. It lasts longer 

Vol. VI. 339 



THE HISTORY AND THE EXAMINATION 113 

if the therapy has been bad. Because it is a subjective rather than an 
objective symptom, it must be inquired about, if possible, without the 
putting of leading questions. In the later stages of untreated or badly 
treated cerebral injuries it appears as an afternoon or evening symptom. 
It may be located at any point in the cranium. Exertion, mental activity, 
emotional stress and liquor all tend to make it worse. Its presence reacts 
unfavorably on the patient's morale and often makes him exaggerate 
the frequency and severity of this symptom. Amnesia or loss of memory 
also will militate at times against obtaining an adequate and correct his- 
tory in these older cases. The loss of memory in respect to length and 
relation to the accident varies from nothing up to a period that antedates 
the accident by some 24 or more hours or weeks afterward. If it can be 
shown unquestionably that the amnesic period started with and followed 
the accident, a period of unconsciousness may be predicated. The doctor 
should be especially careful, however, to verify adequately all claims of am- 
nesia that might have legal implications in order to avoid being a party 
to any intentional deceit by the patient. 

Examination 

In all patients with cranio-cerebral injuries there are certain essential 
objective data that must be determined. These, as with the history, 
are fundamental and apply to any such case. The first is the meas- 
urement of the patient's blood pressure. Both diastolic and systolic 
readings should be taken. From these and the calculated pulse pressure it 
can be determined at once whether or not the patient is in surgical shock. 
If it is decided that surgical shock does complicate the picture, then all 
further measures other than those directed toward its correction are 
contra-indicated. When surgical shock is not present, then the examina- 
tion can be carried further. The second procedure should determine the 
presence or absence of associated major injuries. These two, when taken 
together with the history, will give the doctor the best information in the 
least time about the patient's general condition. 

Next in importance to evaluating the patient's general condition comes 
the settlement of the question as to whether or not the cranial injury is 
one that will permit the introduction of infection into the cranial cavity. 
This, in the majority of instances, necessitates a scalp wound at least and 
an open exposure of the brain tissue at most. The scalp wound alone, 
providing the periosteum is intact, is no more than a scalp wound, even 
though a fracture of the bone lies beneath the intact periosteum. If the 
periosteum is broken, however, and the fracture exposed through the tear, 

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114 CRANIOCEREBRAL INJURIES 

the graver diagnosis of compound fracture must be made. This latter 
implies that infectious material has already entered the bone and is in 
contact with the dura or even the deeper structures. This important 
diagnostic differentiation can be carried out most accurately if the exam- 
iner will insert his sterile finger through the scalp wound and palpate 
the suspected bone directly. This method is infinitely more accurate 
than the use of instruments, retractors or lights and should be used when- 
ever the question of a compounding of a fracture of the skull arises. 
No hesitation should be felt about removing the sutures from a wound 
already closed nor about enlarging a small scalp wound to a point where 
it will admit the examiner's finger. It is better for the patient to have an 
unnecessary scar in his scalp than to develop meningitis or a brain abscess 
because the compounding of a fracture was missed through lack of ade- 
quate examination. To do this, it is not only not necessary but unwise to 
shave the scalp or attempt to clean the wound at this time (see Compound 
Fracture). If a compound fracture is present, its treatment takes prece- 
dence over that for any other associated pathology. The remaining modes 
of entry of infection are found in fractures through the cribriform 
plate into the nose, through the walls of any of the air sinuses, but 
especially the frontal, and through the temporal bone into the external 
ear. The first is a serious surgical complication that requires operative 
relief at the earliest moment that is safe. It is diagnosed by the demon- 
strating of leakage of cerebrospinal fluid from the nose either through the 
posterior nares into the pharynx or the anterior nares onto the upper lip. 
The other two types of fractures do not require emergency treatment, 
and their detailed diagnosis can be safely postponed in the former case 
until adequate x-ray examination can be made, and in the latter until 
more complete data relative to the intra-cranial pressure has been col- 
lected. 

Having made a rough estimate of the patient's general condition and 
determined whether or not potential sepsis and surgical shock are to be 
factors in future therapy, a decision must be arrived at next in regard to 
the measurement of the patient's intracranial pressure and the determina- 
tion of the presence of blood in his cerebrospinal fluid. In the absence of 
surgical shock and a scalp wound this knowledge is indispensable at once. 
In the absence of surgical shock but in the presence of a compound frac- 
ture of the skull it is extremely useful but not immediately indispensable. 
In the presence of surgical shock its acquisition should be postponed until 
after the shock has been corrected. The intracranial pressure can be 
measured in cranio-cerebral injuries only by a manometer attached to a 
lumbar puncture needle which has been inserted into the patient's lumbar 

Vol. VI. 339 



THE HISTORY AND THE EXAMINATION 115 

subarachnoid space. In deeply comatose patients this can be done with- 
out difificulty and the figures obtained with considerable accuracy. If the 
patient is uncooperative and restless, however, the procedure is much 
more difficult and the readings much less accurate. Under these latter 
circumstances the lowest reading should be taken as an approximation of 
the intracranial pressure. Although admittedly an approximation this 
level will serve to indicate the need for, and the amount of, fluid to be 
withdrawn as a therapeutic measure, and this same puncture thus can be 
used as an aid in treatment as well as for diagnosis. The amount of 
cerebrospinal fluid to be withdrawn will depend upon the consequent re- 
duction in intracranial pressure, but even in those cases, in which from 
dehydration, exhaustion or other cause the pressure is below normal 
originally, enough fluid should be collected, not more than Yl c.c, so that 
a gross estimate of its color and, therefore, blood content can be made. 
Attempts to estimate the intracranial pressure by counting the rate of 
drops from the needle or by guessing at the length of the spurt of fluid 
from the same source are indefensible and should never be made. Failure 
to determine the complicating presence of surgical shock or the possibility 
of toxic dehydration before measuring intracranial pressure will lead to 
misinterpretation of the significance of the figures that are obtained. 
Thus a reading of 150 mm. of water on the manometer should be inter- 
preted as normal in the absence of these two factors but in their presence 
may represent not a normal level of pressure but one artificially lowered 
from its true level of 300 mm. of water. Such a reading implies not only 
a different prognosis but also different therapy. 

Thus far the examination has been devoted to the determination of 
certain data that is essential if the doctor's future therapy is to be prop- 
erly conceived and carried out. None can be omitted, and for the pur- 
poses of immediate treatment nothing further need be done, if the 
patient's condition contra-indicates it. However, if a more extensive ex- 
amination is permissible, one should recognize its limitations and avoid 
ascribing too much importance to the individual sign. From the remain- 
ing procedures one can hope only to determine the approximate location 
of the greatest amount of brain injury and some idea of the prognosis as 
far as life expectancy is concerned. For these purposes resort must be 
had to a study of x-ray films of the skull and of the abnormal signs that 
can be elicited by a neurological examination. 

Roentgenology. — To get the full benefit of x-ray films it is essential 
that the physician and the roentgenologist work in cooperation. The 
doctor should not ask the x-ray technician to take films when the patient 
is uncooperative, confused or in surgical shock. Neither should the roent- 

VoL. VI. 339 



ii6 CRANIO-CEREBRAL INJURIES 

genologist consent to interpret films, that he has been forced to take, 
unless they are entirely satisfactory from the technical standpoint, and 
even then he should not allow himself to be led into using these films 
as a basis for therapeutic advice or for the purpose of giving inferential 
opinions about such facts as the degree of intracranial pressure, the 
ascertaining of which lies properly within the sphere of activity of the 
physician. In view of the present tendency by the laity and the courts 
to ascribe undue importance to the taking of x-rays, it is perhaps as es- 
sential to emphasize when not to make such an examination as it is to 
know when information obtainable thereby is unique and indispensable. 
Films are indispensable from the point of view of diagnosis and, therefore, 
of treatment, in only three conditions, and the indispensability is immedi- 
ate in only two of these. Information that is made available in this way, 
and that is most important, has to do with the possible rupture of a middle 
meningeal artery or a large venous sinus. Whenever either of these emer- 
gencies is suspected, the roentgen ray should be used to prove whether 
or not a fracture line crosses either the groove in the temporal bone, 
which carries the artery, or those portions of the occipital and parietal 
bones that cover the lateral and sagittal sinuses and the torquilla Hero- 
philli. Such evidence, added to the previously obtained data that put the 
patient in the class of extradural hematoma suspects, will, by its presence, 
justify early exploratory operation as a final method of confirmation. It 
has been demonstrated that such early operative procedure will prevent 
deaths that do otherwise occur when operative therapy is postponed until 
after the symptomatology has fully developed. When required in unco- 
operative patients, only a single film of the suspected side should be taken, 
sufficient restraint being used to assure the necessary momentary immo- 
bility. Even under such adverse conditions, however, the roentgenologist 
should make every effort to show not only the fracture line but the groove 
in the temporal bone or the shadow of the sinus as well. 

It is equally important, but for other reasons, to know about the 
presence of a fracture line that communicates with or is limited to the walls 
of the frontal air sinuses. They are in direct connection with the nose 
and a break in any of their bony walls that permits communication 
with the meningeal spaces is a potential cause for meningitis or cortical 
abscess. Such a serious possibility, especially when associated with enough 
nasal bleeding or bony displacement to justify the inference that the mu- 
cous membrane lining the sinus has been torn, is an entirely adequate 
reason for early exploratory operative investigation. On the other hand, 
if it can be shown by x-ray that the bony break is limited to the anterior 
wall of the sinus only and does not extend beyond its limits, the cranial 

Vol. VI. 339 



THE HISTORY AND THE EXAMINATION 117 

cavity cannot be involved, and emergency major surgical therapy or in- 
vestigation is contraindicated. 

The third specific indication for x-ray examination of the skull lies in 
the suspected presence of a depressed fracture. This, however, except 
when the regions of the dural sinuses or the meningeal arteries are in- 
volved, does not constitute an emergency as the two others do. X-ray 
examination must be made before adequate therapy can be com- 
pleted, but it need not be done until the patient has recovered sufficiently 
from his associated brain injury to be cooperative and to have a normal 
intracranial pressure. In such cases neither the roentgenologist nor the 
surgeon should be satisfied with anything less than technically perfect 
stereoscopic films of both sides of the head and single flat films, equally 
perfect, taken in both antero-posterior and postero-anterior positions. 

The contraindication to the making of skull films are as definite as 
the indications. They, too, are three in number. The first is the added 
presence of surgical shock. Nothing more than treatment for the shock 
should be done to such a patient until he is out of his shock. This spe- 
cifically includes any form of roentgenology with its attendant exposure 
or moving of the patient. The second contraindication is somewhat less 
definite because it exists only when the first two indications for making 
skull films, mentioned previously, do not interfere, namely suspected rup- 
ture of the middle meningeal artery and fracture into an air sinus. It 
lies in the patient's unwillingness or inability to cooperate with the x-ray 
technician sufficiently to permit the taking of adequate films. Attempts 
to make films under such conditions, other than one special view made 
with minimum restraint, give such poor results that they are of no diag- 
nostic aid, useless added expense to the patient or the institution is in- 
curred, and, worst of all, they favor misinterpretations that may lead to 
untold harm. A physician or surgeon should never ask or expect his 
roentgenologist to take any but single emergency films for one specific 
purpose unless, and until, his patient can cooperate. Finally, third, the 
taking of skull films should be postponed, unless specifically indicated as 
above, while the patient is acutely sick even though he is cooperative. 
The reasons for this are self-evident. 

The indications for taking skull films in all other patients with cranio- 
cerebral injuries are optional from the point of view of the patient's wel- 
fare and treatment and, therefore, should be postponed until such time 
as they can be made most easily. This is usually just before or at the 
time of the patient's discharge from the hospital. This optional type of 
examination is for medico-legal purposes, and even though such films may 
have little or no therapeutic merit, they should be obtained always, pro- 

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ii8 CRANIO-CEREBRAL INJURIES 

viding no harm is done, in order that the patient may not be deprived of 
objective evidence of having been injured. 

Any films other than the two special flat views mentioned above, that 
are taken to demonstrate cranial injuries, must conform to certain stand- 
ards. If they do not, neither the surgeon nor the roentgenologist should 
attempt to make a diagnosis from them. The individual films must be 
contrasting, black and white, and not gray films. They must show not 
only the fracture line, if any, but the grooves for the meningeal arteries 
and the larger sinuses as well. The lateral views must be a true lateral, 
that is, the internal acoustic meati must overlap, and the anteroposterior 
ones must be so taken as to be actually in the sagittal plane, that is, the 
images of the rami of the lower jaws must be duplicates. No less than 
six films must be taken. Stereoscopic views from either side and single 
A-P and P-A films are the minimum. Views of the foramen magnum 
have not proved helpful in my experience. However, views taken to show 
the position of the calcified pineal gland may be very useful. 

Information other than that relative to the presence or absence of a 
fracture of the bone and its relation to vascular markings and air sinuses 
is not ordinarily obtainable from x-ray films. The exceptions occur in 
association with the calcification of an intracranial clot, usually subdural; 
the comminution of the fracture, of no therapeutic significance; the 
coincidence of the fracture with a suture line, commonly miscalled dias- 
tasic fracture; the misinterpretation of the normal forking at the mastoid 
end of the lamdoidal suture as a fracture line and the attribution of diag- 
nostic significance to scalloping or convolutional markings in the film, 
despite the fact that their etiology is unknown and their presence demon- 
strably coincidental. 

X-rays taken long after the receipt of the skull injury may be subject 
to dispute as to their value as evidence of fracture. It will be claimed 
that the predicated fracture line is invisible at a later date because the 
bone has healed in the interval. This is an undoubted possibility. It is 
more likely to happen in children than in adults, in linear as opposed to 
other types of fractures, and if the pericranium has been kept intact than 
if it has not. Even depressed fractures have been known, rarely to be 
sure, to have healed in such a way as to produce what is to all appear- 
ances a normally intact inner table. The time necessary to effect com- 
plete healing in any cranial fracture varies from months to years, and it 
may never take place at all. Fibrous union, however, always takes place, 
and from the point of view of function is as satisfactory as the bony type. 
Fracture lines in which the dura is incarcerated never heal at that point, 
as far as is known, until the dura is removed. Separation of the sutures 

Vol. VI. 339 



THE HISTORY AND THE EXAMINATION 119 

is of no diagnostic significance in these acute injury cases after the patient 
is more than two years old. 

The Localization of the Point of Maximum Brain Injury. — This usually 
is impossible except as an approximation. Since any or all signs may be 
completely misleading at times, the best that one can hope to do is to 
lateralize the injury. Its placement in the anteroposterior direction can 
be little more than a guess. To do even this, a careful neurological exam- 
ination is essential. Experience has shown that if, in the course of this 
examination, certains signs are elicited, they can be allowed to carry a 
little more localizing or prognostic weight than the average. Those of 
localizing significance are: (i) A generalized rigidity in extension. This 
means decerebration from extensive mid-brain damage. The prognosis is 
inevitably fatal. (2) Aphasia. This must be interpreted, however, in the 
light of the patient's right- or left-handedness and especially from the point 
of view of language difficulty due to lack of education or foreign birth. 
It points to a temporofrontal lesion. (3) A facial palsy of the central 
type. This either alone or in combination with aphasia has indicated the 
side of the subdural hematoma with considerable frequency. (4) Dilata- 
tion of one pupil. This is an unreliable localizing sign. It has been shown 
to occur as frequently opposite to as on the same side as the brain lesion. 
(5) Pathological reflexes. These are not reliable indicators even if they 
are unilateral. (6) A hemiplegia. This may be present on the same side 
as an expanding lesion as well as on the opposite side. This confusion 
arises because the brain is moved laterally by the big clots far enough to 
allow the opposite edge of the tentorial incisura to compress the opposite 
pyramidal tract before its fibres cross in the pons. (7) Complete blind- 
ness with a loss of the light reflex in one eye means a division of that 
optic nerve anterior to the chiasm. (8) Papilledema is rare before 10 to 
14 days after the injury. (9) A stiff neck may be due to blood and not 
infection in the meningeal spaces. 

From the prognostic point of view, the following may be helpful : 
(i) The depth of coma. This is an indication of the severity of the in- 
jury but has no further prognostic significance. It should be measured 
by the patient's response to definite purposeful stimuli. (2) General 
muscular flaccidity and (3) relaxation of the anal sphincter both are 
very bad prognostic signs. (4) Retention of urine with an overflow blad- 
der is unfavorable but (5) periodic complete emptying of the bladder 
usually indicates a lessening of the coma. (6) Sudden fixed dilatation of 
both pupils is a terminal symptom. (7) Respiratory irregularity, especi- 
ally if it succeeds stertor and is followed by any type of Cheyne-Stokes 
rhythmicity, means an advancing lesion which usually will terminate in 

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I20 CRANIO-CEREBRAL INJURIES 

death within a few hours. It is due to medullary edema. (8) Circula- 
tory failure, more particularly in old people, usually is evidenced by 
peripheral cyanosis and, at the end, by edema and what appears to be a 
bronchopneumonic process in the lungs. There may be no cardiac irregu- 
larity except at the end. The pathology seems to be primarily that of 
increasing tissue anoxemia. Arteriosclerosis with previous irregular meth- 
ods of living, anemia, inhalation anesthetics, the administration of large 
amounts of barbiturates and, frequently, accidental or therapeutic toxic 
dehydration all predispose to this condition. It is an extremely bad 
prognostic sign. 

General Principles of Treatment 

There are certain general principles of treatment that apply to all 
patients with cranio-cerebral injuries regardless of the individual path- 
ology. They have to do with nursing problems, the care of the skin and 
viscera, the necessary use of drugs and the therapy that arises out of 
those miscellaneous complications produced as the result of various nerve 
palsies. They should not be neglected in favor of the more spectacular 
procedures that apply more directly to the pathology itself. 

Nursing ■ 

The presence of a competent nurse in attendance on a patient with a 
cranio-cerebral injury may make the difference between a recovery and 
a fatality. This does not imply a knowledge of drugs or medicine or sur- 
gery on her part, but it does imply the ability to control her patient with 
a minimum of mechanical aid; to eliminate such harmful influences as 
excessive noise or light, to recognize the importance of a wet bed, un- 
natural positions of paralyzed limbs and the early development of con- 
tractures and to control family and friends from the point of view of the 
best interests of the patient. All or any of these requirements necessitate 
an even temperament, a sense of the importance of little things and a 
willingness to subordinate what might be called the profession to the art 
of nursing. 

Noise, Light, Heat and Cold 

Patients with cranio-cerebral injuries are particularly susceptible to 
the effect of external stimuli. The absence of noise about such an individ- 
ual makes it much easier to keep him quiet and, therefore, provides him 
with a better chance to recover. Included among noises must be that 

Vol. VI. 339 



GENERAL PRINCIPLES OF TREATMENT 121 

made by the conversation of anxious relatives and friends. If possible, 
they should be excluded from the patient's room until he is again rational. 
If this proves to be impossible, they should be so placed that he cannot 
see them, and they must be absolutely silent. Bright light has the same 
stimulating effect that noise has. This applies particularly to sunlight 
and unshielded electric lights. They and other similar sources of illumi- 
nation should be excluded insofar as possible. External heat should be 
applied to the patient only when he is cold. Thus, it should not be used 
in the face of a high temperature even though the clinical diagnosis may 
be surgical shock. The resultant sweating and other loss of body fluids 
well may add a complicating toxic dehydration to a situation that is al- 
ready complex enough. Reduction of abnormally high temperatures, such 
as those seen in association with the hyperthermia of medullary edema, 
may be attempted but usually is of little avail. However, attempts should 
not include cold sponges or cold packs. Such applications contract all 
surface vessels. The only possible means of reducing these high tempera- 
tures inside the body is by the transfer of the heat therein to, and its sub- 
sequent irradiation from, the surface. The transfer is by means of the 
blood stream, and the irradiation is from the surface vessels. Both these 
processes will be facilitated by procedures which dilate the surface vessels 
and impeded by those that contract them. The preferred method of 
dealing with such hyperthermia is to keep the surface of the body moist 
with fluid at normal body temperature. This will insure the delivery of 
blood to the surface. This, in combination with some method for evapo- 
rating this fluid, will promote irradiation and thus cooling. Exposure of 
the wet body to a gentle breeze from an electric fan fulfills these condi- 
tions. Temperatures can be reduced in this way 5° or 6° in an hour. It 
is customary to apply an ice-cap to the head of all patients suffering from 
a cranio-cerebral injury. My experience has been that this procedure is 
without therapeutic merit. Its only conceivable use is to render the pa- 
tient willing to keep his head somewhat quieter than he would otherwise, 
because of his subconscious desire to successfully balance the cap and to 
thus avoid the imagined disorder that might follow its fall. 

Position of Patient 

A comptetent nurse will never permit her patient to remain in an 
awkward or uncomfortable position unless forced to do so because of 
necessary restraints. If there are paralyzed extremities, this precaution 
h doubly necessary. Over-flexion of the hands at the wrist, over-extension 
of the feet at the ankles, embarrassment of respiratory movements from 

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122 CRANIOCEREBRAL INJURIES 

the weight of a paralyzed arm which is lying on the chest or abdomen and 
the imposition of the weight of the body on an arm or leg for even the 
shortest amount of time, all must be constantly watched for and studi- 
ously avoided. A cradle always should be placed in such a way as to 
keep the bed clothes off the feet. Any signs of contracture should be re- 
ported at once in order that appropriate corrective apparatus can be ap- 
plied early. There is disagreement as to whether such a patient's head 
should be kept above or below the level of his pelvis. Those who advo- 
cate the head-high position claim that it reduces intracranial pressure 
because of the effect of gravity on the cerebrospinal fluid. On the other 
hand, their opponents claim that such a position compresses the jugular 
bulbs under the weight of the brain and promotes cranial venous conges- 
tion and thus increases intracranial pressure. These latter believe, there- 
fore, that the patient's head should be lower than his pelvis. My ex- 
perience leads me to believe that in young, conscious, cooperative patients 
that position which is most comfortable is the preferable one. This usu- 
ally means the head-low. There need be no hesitation, however, in chang- 
ing to the head-high, if the patient wants to. In all other cases the 
position of the head in relation to the pelvis depends upon such factors 
as the circulation, respiration, paralysis of deglutition, other injuries and 
so forth. It is especially important, however, to see to it that elderly pa- 
tients are placed in a sitting position in bed at the earliest possible moment. 

Restraints 

It can be stated as a general rule that in patients with cranio-cerebral 
injuries the fewer restraints the better. Their use should be only for the 
purpose of preventing the patient from doing himself harm. This will 
include preventing him from falling or getting out of bed, from removing 
dressings over wounds, splints from his extremities, intravenous drip 
needles from his veins and the stomach-tube from his stomach. Within 
these limits he may have, and will do better if he has, complete freedom 
of motion. When applied, the restraints should be efficient and should 
accomplish only the purpose for which they are put on and nothing more. 
The use of a strait-jacket to keep him from taking off a bandage, for 
example, cannot be condemned too strongly. The production of such 
artificial immobility in this or any other way defeats the purpose of re- 
straint. Immobility is accomplished only after the patient has fought 
himself into a state of exhaustion in his efforts to escape. Thus he has 
harmed himself much more than he could possibly have done if he had 
been given complete freedom. Whether used with or without mechanical 

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GENERAL PRINCIPLES OF TREATMENT 123 

aid, the influence of the nurse must not be neglected. If she will exercise 
a little tact and gentle persuasiveness, if she will be patient and entirely 
reasonable and unemotional at all times, it will only be necessary to use a 
minimum of mechanical aid to effect reasonable limitation of activity. In 
particular it should be emphasized that it is absolutely inexcusable to 
combat the patient's lack of cooperation by brute force. 

There are many types of acceptable restraints. The most useful are 
bed-sides. They may be of metal, wood or canvas. I no longer use any- 
thing but canvas. This type comes in two pieces and is made from heavy 
awning material or sail-cloth. Each piece measures 6 feet in length 
and slopes from a width of 28 inches at the head of the bed to a width 
of 18 inches at the other end. All edges are perforated by metal-lined 
holes at appropriate intervals. When in use, the outer edge of each 
piece of canvas is laced to the bed-frame and the lower and upper ends 
to the foot and head-pieces respectively. The centre edges are then tied 
together at their lower ends and thereafter pulled together with lacing 
as high up toward the head of the bed as is necessary in order to keep 
the patient beneath them. Rope is the best lacing material. If the patient 
persists in crawling out from under this and getting out of bed, it will 
be necessary to restrain his feet. This is done by wrapping the ankles 
with flannel over which is tied folded sheeting. The free ends of the sheet- 
ing are fastened to the foot-piece of the bed at its midpoint and with the 
feet close together. The hands can be restrained in a similar way except 
that the sheeting should be tied to the bed-frame at either side. Ex- 
tremely obstreperous cases may have to have a folded sheet pulled tightly 
across their chest, or thighs, or both and then fastened to the bed-frame 
on either side. This should constitute the maximum, however, and should 
be needed rarely and then for short periods of time only. 

Care of the Skin, Mouth, Lips, Teeth and Hair 

The condition of the patient's skin, especially over weight-bearing bony 
points, has long been recognized as the test of successful nursing. This 
has been particularly true in regard to individuals with spinal injuries and 
holds no less true in relation to those with severe cranio-cerebral damage. 
The lesions of the skin, when they develop, range all the way from a 
transitory redness over bony prominences to an actual loss of tissue from 
ulceration and secondary infection. The skin over the sacrum, the iliac 
crests, the heels, elbows, the region of the scapulae, the back of the head 
and even the upper dorsal spinous processes are the sites that are most 
commonly involved. Local applications vary with the nurse and nursing 

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124 CRANIO-CEREBRAL INJURIES 

school, and all that I have seen in use have proved equally satisfactory. 
None of them, however, can be or are satisfactory unless certain basic 
requirements are met. These are three. The most important is the pre- 
vention of maceration of the skin. Maceration follows pressure on wet 
skin. It may develop within 30 minutes in favorable cases. To avoid it, 
the bed must be kept constantly dry. If it gets wet, it must be changed 
at once, the wet skin washed, dried, rubbed with alcohol and well pow- 
dered. Next in importance is the prevention of excess local pressure over 
any bony prominences. This is most apt to develop in hemiplegic or 
comatose patients. To prevent it, the patient must have his position 
constantly shifted. This should be done on schedule and in such a way 
that all weight-bearing points share equally. I have found that air-rings 
or homemade doughnuts are not only not satisfactory, but are harmful. 
Instead, I use a single lambskin tanned with the wool on and with the 
wool side against the skin. This is placed beneath the buttocks and lower 
back. It should be washed, sterilized in lysol solution and then dried 
before use. If two or more are available, dirty skins can be replaced at 
once and yet a clean one be always available. Smaller pieces may be 
used also under other points of pressure such as the heels, back of the 
head and so forth. Finally, skin irritation from friction must be avoided. 
This is prone to develop in restless uncooperative patients and is most 
apt to affect the shoulder-blades, elbows and the back of the head. The 
local use of a piece of lambskin, as noted above, constant nursing atten- 
tion and such therapy as will take care of the underlying brain pathology 
are the best methods of care and prevention. 

Much comfort is derived from adequate care of the mouth, lips and 
teeth. They should be cleaned regularly, and the lips in particular should 
be kept soft and free from sores. 

The hair, especially in women, must not be neglected. When it is long 
and tangled, matted with blood or vomitus, or allowed to remain undis- 
turbed beneath a bandage, it is a source of worry and great discomfort to 
its owner. It should be combed and cleaned, the worst parts being sacri- 
ficed if necessary, and bandages, if any, so applied as not to include long 
hair if it is at all possible. Daily care thereafter should prevent any re- 
currence of this disorder. 

Food and Fluids 

There is no limit to the type or quantity of food that these patients 
may be given other than its caloric, chemical or vitamin content and their 
capacity and willingness to eat it. 

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GENERAL PRINCIPLES OF TREATMENT 125 

It is essential in the care of these cranio-cerebral injury cases to have 
some knowledge of their fluid intake and output. In the case of the out- 
put, this can only be an approximation, but even so the figures are signifi- 
cant and helpful. The measurements should be for 24-hour periods in 
either c.c. or ounces. They should then be plotted on the temperature or 
other chart in the form of a graph. Much of their significance is lacking 
otherwise. The amount of fluid intake per 24-hour period should be speci- 
fied by the physician. The nurse, however, carries the responsibility of 
seeing that the patient takes that amount and also of collecting, measuring 
and recording the fluid he puts out. Fluid is best administered by mouth 
and need not necessarily be limited to varieties that have no caloric or 
vitamin content. Oral administration can be supplemented by intrave- 
nous drip, subpectoral infusions, in small children by intraperitoneal in- 
fusions or clysis and finally with the aid of a Rehfuss or similar tube 
inserted through the nose. 

Care of the Urinary Bladder 

Although anatomical abnormalities of the urinary bladder are not 
associated with cranio-cerebral injuries except possibly in the ante-mortem 
state, micturition does not necessarily take place in a normal manner 
when there is any significant loss of consciousness. This probably is due 
to a psychological inhibition of the emptying contractions and results in 
the production of an over-flow bladder with retention. This must be un- 
comfortable and does actually produce a high degree of restlessness which 
is promptly relieved by catheterization. If the unconsciousness continues 
for a long time and repeated catheterizations are necessary, it is better 
to make use of a tidal drainage apparatus. Although this requires an 
indwelling urethral catheter, it prevents the accumulation of residual 
urine and the atony that is associated with overstretching of the bladder 
wall. The cystitis that necessarily accompanies an indwelling catheter 
after 72 hours is of no moment as long as no residual urine collects. It 
will clear up in a few days after the catheter has been removed. 

When loss of consciousness is so profound, however, as to exclude any 
action on the spinal reflexes by the higher centres, the bladder becomes a 
pure reflex type. Under such circumstances, it will empty completely in 
response to a given amount of fill. This will occur inevitably and regard- 
less of the time element. Repeated catheterization, therefore, is notori- 
ously unsuccessful as a means of keeping such cases dry. They can only 
be handled by being put on tidal drainage, and the sooner that is done, 
the less likely they are to have bed-sores. 

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126 CRANIOCEREBRAL INJURIES 

In moribund patients the bladder reverts to the atonic form, the ex- 
ternal sphincter is flaccid, and an overflow retention is present. 

Care of the Large Bowel 

The care of the large bowel presents no extraordinary problem. The 
proper use of enemata and cathartics will assure normal functioning. 
Care should be exercised to make sure that an impaction does not occur in 
the rectum. Incontinence is an ante-mortem symptom associated with a 
flaccid anal sphincter. 

Care of the Eyes 

The final responsibility for the care of injuries to the orbit or its con- 
tents in patients with cranio-cerebral injuries should be placed on the 
shoulders of a consulting ophthalmologist. Orbital, periorbital and sub- 
conjunctival hematomas are frequent and, if carelessly or improperly 
treated, may lead to permanent impairment of the patient's sight from 
corneal scars. If, in addition, there is protrusion of the eye-ball, severe 
conjunctival edema or chemosis, this danger is materially increased. 
Temporary therapy should include the instillation of sterile oil into the 
conjunctival sac, the assurance of an abundant supply of moisture to the 
conjunctiva, if it is dry, by the application of an air-tight goggle, the use 
of cold compresses locally to reduce the swelling and especially the avoid- 
ance of direct contact between the cornea and compresses or bandages. 
An associated facial or trigeminal palsy renders such measures and the 
care used in applying them until the arrival of the ophthalmologist doubly 
important. 

Care of the Ears 

If, as a complication of a cranio-cerebral injury, there is blood or cere- 
brospinal fluid draining either alone or as a mixture from the patient's 
ear or ears, great care must be taken to prevent the entrance of infection 
into the meningeal spaces through any fracture that may be present. To 
accomplish this, it is of utmost importance that the ear canal be neither 
irrigated nor packed. If the former is done, infection may be washed in, 
and if the latter, infection that is already present in the inner or middle 
ear and that would otherwise cause no trouble, may be dammed up suf- 
ficiently to cause it to spread inward rather than drain outward. Blood 
clots in the canal should not be disturbed until all drainage has been ab- 

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GENERAL PRINCIPLES OF TREATMENT 127 

sent for 10 days and then only with the greatest of care and preferably 
by an aural consultant. Cerebrospinal fluid drainage is best controlled by 
measures, such as repeated lumbar drainage, that reduce the intracranial 
pressure to normal and keep it there. While it is theoretically possible 
for a permanent aural cerebrospinal fistula to form and require closure by 
operation, I have never seen it. It is important to remember that, with 
rare exceptions, persistent leakage of cerebrospinal fluid from the ear does 
not decompress the brain but instead is evidence of persistent high intra- 
cranial pressure. 

There is no treatment for the deafness that may follow these injuries. 

Traumatic or hemorrhagic labyrinthitis may be associated with cranio- 
cerebral injuries. It tends to get well of itself and is due to a fracture 
and hemorrhage into the internal ear. Vertigo, especially on turning the 
head, is the usual evidence of its presence. If it persists, and provided 
the disability is extreme, a section of the vestibular nerve in the posterior 
fossa of the skull may be expected to give some measure of relief. This 
should not be undertaken until at least 8 to 12 months after the injury. 

A loss of the sense of taste frequently is associated with cranial fractures 
that involve the ear and tends to be permanent. There is no treatment. 

Care of the Nose 

Either bleeding or leakage of cerebrospinal fluid from the nose in as- 
sociation with cranio-cerebral injuries is an extremely important sign. The 
latter inevitably points to a fracture so placed that the cavity of the nose 
is in direct communication with the meninges and brain. As long as such 
a fistula remains open, meningitis at some time is a certainty. It can only 
be closed by a major operative procedure, which nevertheless must be 
carried out at the earliest moment that the patient's condition permits. 
This fracture usually is, in part at least, through the cribriform plate, and 
the fistula exists because an open funnel of dura and arachnoid has been 
caught and incarcerated in the fracture line. Lumbar punctures will 
neither close this fistula nor stop the rhinorrhoea. Unlike the ear fistulse, 
enough cerebrospinal fluid may be lost through leakage to reduce the in- 
tracranial pressure to very low levels even in the total absence of lumbar 
drainage. Until operative closure can be carried out, all plugging and 
irrigation of the nose, blowing of the nose, sneezing, coughing and deep 
breathing must be prohibited. If the patient is kept flat in bed constantly 
and whenever there is bleeding from the nose, the diagnosis may be 
missed. In the former instance the cerebrospinal fluid may leak directly 
into the posterior pharynx and be swallowed, and its presence thus be 

Vol. VI. 339 



128 CRANIOCEREBRAL INJURIES 

unnoticed until the patient's head is raised. In the latter case the pres- 
ence of the blood may mask the presence of the fluid. The precautions 
noted above must be observed strictly in the presence of nasal hemorrhage 
or suspected fractures of the frontal fossa until the absence of this cerebro- 
spinal rhinorrhea can be definitely proven. Once the fistula is proven 
absent or closed by operative procedure, ordinary measures to cleanse the 
nose may be adopted, but not before. Sulphanilamide in appropriate 
dosage should be started whenever the presence of rhinorrhea is sus- 
pected. 

The Complications Arising Out of Various Cranial Nerve Palsies 

Facial paralysis is a common complication of cranio-cerebral injuries. 
It may be either central or peripheral in type, usually the latter. Its 
presence calls for particular care of the eye. This has been discussed 
above. In addition massage of the facial muscles by stroking upwards 
from the corner of the mouth toward the outer canthus of the eye, electrical 
stimulation and, if necessary, various types of plastic supportive opera- 
tions on the facial tissues will prove useful. If it can be determined that 
the nerve has been injured in the Fallopian canal, it may be decompressed 
or repaired locally, and, if this is not feasible, or the location of the break 
not known, the distal end may be anastomosed with the proximal end of 
either the spinal accessory or the glossopharyngeal nerve. Neither of 
these anastomoses is entirely satisfactory, however, because, when suc- 
cessful, the voluntary contraction of the facial muscles is accompanied 
always by a varying number of associated movements of the shoulder, 
side of the neck or tongue. The more radical operative therapy should 
never be undertaken unless, and until, all other procedures have failed 
completely and only when the surgeon is convinced that the interruption 
is anatomical and regeneration impossible otherwise. 

Loss of hearing, either with or without loss of sense of taste and dizzi- 
ness, may be associated with injury to the eighth nerve. These and other 
points connected with damage to the facial nerve have been discussed 
sufficiently already under the heading Care of the Ears. 

Oculomotor palsies of all degrees are a common accompaniment of 
cranio-cerebral injuries. The most usual is a paralysis of lateral gaze due 
to injury to one sixth nerve. Third nerve palsy may occur also and be 
manifested at first by a dilatation of the pupil only. Ptosis of the upper 
lid either may appear later or may not develop at all. Complete ophthal- 
moplegia is observed rarely. These is no particular treatment of the eyes 
themselves, other than symptomatic, that is of any value. As much 

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GENERAL PRINCIPLES OF TREATMENT 129 

therapy as is possible is carried out when the causative cerebral lesion is 
diagnosed properly and therefore treated properly. Prognosis in regard 
to the recovery in any individual instance is unpredictable, but hope for 
resumption of function should not be abandoned for at least a year after 
the receipt of the injury. Treatment, after it has been demonstrated that 
the paralysis is permanent, should be left in the hands of a competent 
ophthalmologist. 

Division of the optic nerve between the chiasm and the back of the 
globe occurs fairly frequently. It is accompanied by immediate blindness 
as well as a loss of the light refiex. Treatment obviously is of no avail. 
It is important, however, to recognize the presence of this complication 
and to notify the patient or his legal representative of it at the earliest 
possible moment. Only in this way can false claims for damages based 
upon alleged improper treatment by the physician or allegations of fraud 
and malingering on the part of the patient be combated successfully. 
Above all, the physician should not expect the patient to be the one to 
first recognize his loss of sight. 

Doubtless any other cranial nerve can be damaged to any degree in 
association with cranio-cerebral injuries. The occurrence rate, however, 
is so low, except as noted above, that detailed discussion of the resulting 
symptomatology and consequent treatment has no practical value. 

Drug Treatment 

The most important single fact about the use of drugs in the treat- 
ment of cranio-cerebral injuries may be epitomized in the following sen- 
tence: Never give morphine in the presence of an actual or a suspected 
increase in intracranial pressure. A usual cause of death in cranio-cerebral 
injuries is a respiratory paralysis which is due to medullary edema and 
depression of the respiratory centre. A usual action of morphine is the 
depression of the respiratory centre. When a patient already is in danger 
of dying because of a depression of his respiratory centre, it is worse than 
foolish to insure death from respiratory failure, even if it is dignified by 
the name of treatment, by administering a drug that acts by depressing 
the respiratory centre. 

The over-expenditure of energy by restless patients is, however, harm- 
ful. Drugs in addition to treatment directed specifically against the cere- 
bral injury, the use of restraints, judicious nursing and so forth, may be 
essential to prevent such activity. The barbiturate preparations usually 
prove to be the most useful drugs under such circumstances. The ones 
that are most efficacious are phenobarbital (luminal) by mouth, pheno- 

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130 CRANIOCEREBRAL INJURIES 

barbital sodium (luminal sodium) intravenously, and pentobarbital sodium 
(nembutal-intravenous) intravenously. All of these, when given by 
mouth, will act more slowly but over a longer period of time than when 
given by vein. The usual dosage follows: — Phenobarbital gr. \}/2 (o.i 
gm.) by mouth 2 or 3 times a day. Phenobarbital sodium, enough intra- 
venously to produce immediate sleep; as much as gr. 10 (0.6 gm.) has been 
given in this way in an adult, but this is unquestionably a high maximal 
dose. Pentobarbital sodium, enough intravenously to produce immediate 
sleep; less than gr. 7 (0.5 gm.) for an adult usually is required. Strychnine 
is to be given in case of an overdose of barbiturates. It should be given 
in doses of gr. 3^^o (2 mgm.) intravenously and repeated as indicated. 
There is, at present, some evidence to show that excessive use of the bar- 
biturates can produce a toxic anoxemia which, in certain cases, will prove 
fatal. 

Paraldehyde by rectum or, in extreme cases, intravenously is a useful 
soporific. Dr. 6 to 8 (24 to 32 c.c.) in 4 ounces (120 c.c.) of starch solu- 
tion is the adult dose, when given by rectum, and an average of i dr. 
(4 c.c.) but not more than 2 dr. (8 c.c.) in a single dose when given intra- 
venously. 

For headache a combination of codein gr. ^ (30 mgm.), aspirin gr. 10 
(0.6 gm.) frequently will be effective after all other and more complicated 
remedies have failed. This dose can be repeated every 4 hours until relief 
is obtained. Tribromethanol (avertin) is contra-indicated in these cases 
except when used as a basal anesthetic. Sulphanilamide (prontolin) 
should be given whenever an infection with a streptococcus hemolyticus or a 
meningococcus is either suspected or proved. The dosage must be suffi- 
ciently large at first and then so graded as to produce and maintain a 
concentration in the blood at 10 mgm. per cent, or higher. In men- 
ingococcus meningitis it is well to use antimeningococcus serum beside 
sulphanilamide. It may prove useful too when treating pnetimococcus men- 
ingitis, especially if proper type specific serum also is available and used. 
With all of these infections, the blood concentration of the sulphanilamide 
must be kept at the higher levels so long as severe symptoms of toxicity 
of the drug do not develop. 

The most dependable stimulants are caffeine, strychnine and coramine. 
Caffeine should be given intravenously in 73^^ grain (0.5 gm.) doses. 
This may be repeated every 2 hours or oftener. It is of absolutely no use 
when given in any other way. Strychnine also should be given intrave- 
nously. The dose should be gr. 3^^o (2 mgm.) which may be repeated every 
2 hours for 4 to 6 doses. The amount should be reduced thereafter and 
care should be taken not to prolong its use to the point of producing 

Vol. VI. 339 



METHODS OF TREATMENT 131 

muscular twitching. Botii these drugs and especially caffeine are useful 
in the treatment of a failing circulation or to stimulate respiration. 
Strychnine is useful in case of barbiturate poisoning and will prove useful 
in bringing the deeply comatose patient closer to the conscious level. 
Coramine is a drug for strictly emergency use. It is given intravenously 
and the dose is i ampoule. The ampoule contains 5 c.c, of a 25 per cent, 
aqueous solution. It is a strong respiratory excitant and is helpful in 
tiding over a sudden respiratory emergency, which will be ended by a 
decompression, a ventricular puncture or some similar procedure. I have 
never used more than one ampoule. 

Methods of Treatment 

In addition to the general methods of treatment necessary for the care 
of any major or minor surgical condition there are certain special proce- 
dures that are peculiar to the care of patients suffering from cranio- 
cerebral injuries. For convenience of reference all of these are grouped in 
this one section. No attempt will be made to relate any special procedure 
to any given type of injury. That will be covered in succeeding sections 
which deal with the individual injuries under appropriate diagnostic head- 
ings. In general, methods of treatment of cranio-cerebral injuries are 
either operative or non-operative. The non-operative procedure will be 
dealt with first and in some detail. Operative methods will not be de- 
scribed, since the more detailed technical minutiae are peculiar to the needs 
of the surgeon in contradistinction to those of the physician. 

Non-operative Methods of Treatment 

Lumbar Puncture. — The most universally applicable therapeutic and 
an indispensable diagnostic procedure for handling any and all types of 
cranio-cerebral injuries is the lumbar puncture. In acute injuries of the 
skull and its contents, its use is entirely without danger regardless of the 
degree of intracranial pressure. Many thousands of lumbar punctures 
have now been done in such cases^ and no verified case has come to light 
in which it has been shown by post-mortem or equally accurate study that 
the lumbar puncture did in fact cause death. From the point of view of 
therapy it has been shown by a study of two parallel series of cases treated 
by all members of the surgical staff of a large municipal hospital that an 
increase in the therapeutic use of lumbar puncture of only 4 per cent, was 
associated with a decrease in mortality of about 13 per cent. The total 
number of cases studied was 983 and the period covered 4 years. 

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132 CRANIOCEREBRAL INJURIES 

To be safe and, particularly, to be either therapeutically or diagnos- 
tically significant, a lumbar puncture must be done properly, proper equip- 
ment must be used, and the operator must have some idea of what 
information is obtainable. If these criteria are not followed, the data will 
be incomplete, inaccurate, unreliable and may lead to diagnostic errors 
that will seriously jeopardize the patient's chances. 

The Interpretation of Lumbar Puncture Findings. — Of all the data 
made available by a lumbar puncture in a case of cranio-cerebral injury 
that relative to the intracranial pressure is most liable to misinterpreta- 
tion. Since it is known that either surgical shock or toxic dehydration 
will reduce intracranial pressure to artificially low levels, the pressure 
measurements obtained by lumbar puncture must be considered in the 
light of these facts. Thus, it is essential to have blood pressure readings 
and an adequate history of the fluid intake. This latter must include 
statements relative to exposure to heat, fever, vomiting, consciousness 
and, if at all possible, some estimate of the amount of fluid intake and 
urinary output for at least one and better more than one 24-hour period. 
If it can be shown that toxic dehydration is a possibility, or that surgical 
shock is present, the finding of a subnormal intracranial pressure will 
confirm that finding, a normal reading will point to an actual increase 
and a high reading to even higher levels of pressure. Both prognosis and 
treatment must be modified accordingly. 

The finding of white blood cells in the removed specimen of cerebro- 
spinal fluid does not necessarily indicate a meningeal infection. The pres- 
ence of blood in the cerebrospinal fluid may set up a pleocytosis which 
will clear up after the red corpuscles have been destroyed or removed. A 
better indication for the presence of a meningeal infection is found in a 
study of the sugar and chloride content of the fluid. 

If the first lumbar puncture is done some days after the receipt of the 
injury or after enough time has elapsed to permit the destruction of the 
red blood cells in the fluid, a measurement of the total protein content 
may serve as an indicator of a previous admixture of blood. In the cases 
with large amounts of added blood the fluid will be yellow, but even in 
those cases in which the added blood has been too small in amount to be 
grossly visible later as a yellow discoloration, its presence may be detected 
and deduced by and after a measurement of the total protein content. 

Therapeutic Dehydration 

Therapeutic dehydration may be accomplished by the administration 
of appropriate solutions either by mouth, by rectum, by vein and, in the 
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METHODS OF TREATMENT 133 

new-born, intramuscularly. Regardless of the method used, however, the 
effect on the brain will be limited to a reduction of its volume. It is ap- 
parent, therefore, that the intracranial pressure will be reduced only in so 
far as the brain shrinks and that that modicum of pressure that is due to 
mechanical blockade of the arachnoidal villi by free blood cells in the 
subarachnoid fluid cannot and will not be altered. 

Dehydration by Mouth. — This method is of interest only for purposes 
of record. A sufficient number of appropriately sized doses of a saturated 
solution of magnesium sulphate is given to produce several watery bowel 
movements in each 24-hour period. It is useful for its psychological ef- 
fect only. 

Dehydration by Rectum. — This method has a distinct place in the 
therapy of cranio-cerebral injuries. If a proper technique is used, a 
rather slow and prolonged dehydration can be produced. A saturated 
solution of magnesium sulphate is used, the solution being given into the 
patient's rectum by gravity only. Two ounces (60 c.c.) is the average 
dose for an adult, but this may be varied in either direction. The maxi- 
mum should not exceed 4 ounces, however. After the solution has been 
introduced, the catheter should be clamped off and left in place. The 
solution need not be warmed before use, and there is no necessity for the 
use of any opium derivative locally. On no account should its instillation 
be preceded by a cleansing enema. This procedure may be repeated once 
every 3 hours for 4 doses or once every 4 hours for 3 doses. Twelve 
hours should intervene between each series regardless of the amount used. 
In the new-born no more than i drachm of the solution should be given 
at any one time. The drug is not given as an enema. The patient should 
be informed of this and urged to retain his rectal contents as long as possi- 
ble. A note should be made of the length of time the solution is retained. 
Toxic dehydration can be produced by prolonged or injudicious use of this 
therapy. Associated limitation of fluid intake is of no therapeutic value. 

Dehydration by Vein. — This is the most useful and the most rapid 
method of producing dehydration. Ordinarily a 50 per cent, solution of 
glucose is used. Because such a solution acts by increasing the tonicity 
of the blood stream and thus withdrawing by osmosis fluid from the 
tissue spaces into the vascular tree, it is also useful as a means of treating 
surgical shock. Indeed, this therapy has proven second only in efficiency 
to the transfusion of properly matched blood, since it raises systolic blood 
and pulse pressures and prevents further escape of serum through leaking 
capillaries. Hypertonic salt solution originally was recommended as the 
preferred intravenous dehydrator, but experience soon showed that, be- 
cause it was a solution of electrolytes, it became isotonic and left the 

Vol. VI. 339 



\ 



134 CRANIO-CEREBRAL INJURIES 

vascular tree very quickly. This served only to increase the tissue edema 
and to make already bad matters worse. More recently, certain writers 
have advocated the use of a solution of sucrose as the preferred intrave- 
nous dehydrator. The only objection to this is the fact that it is more 
difificult to obtain when the physician needs it in an emergency in an out 
of the way place. Glucose solution, despite reports of animal experimen- 
tation to the contrary, does not produce a secondary edema like salt 
solution, and unlike sucrose it is obtainable now in an immediately usable 
form at practically any drug store no matter where located. 

When glucose is given therapeutically into a vein, certain precautions 
must be observed especially in regard to the commercial solutions. The 
injection must be made slowly, and great care should be taken to see that 
none of the hypertonic solutions get into the perivenous tissues. If this 
happens, a considerable degree of sloughing with scars that are disfiguring 
and slow to heal is liable to follow. The syringe should be as nearly as 
possible chemically as well as surgically clean. In particular Ringer's 
solution should not have been used recently in the syringe, nor the syringe 
wiped with sized cotton cloth or gauze before putting the glucose in it. 
The buffer in the commercial sterile solutions will precipitate if brought 
into contact with the calcium that is easily mobilized from both Ringer's 
solution and sizing. Such a precipitate may cause severe reactions if in- 
troduced into the blood stream of a patient. For the same reason if 
distilled water is used to make solutions of higher dilution, it must be 
free from room dust and have been collected from a dust-proof, recently 
emptied still. The very hypertonic solutions usually cause thrombosis of 
the vein at the point of administration. Ignorance of this possibility may 
lead to unnecessary delay in giving subsequent infusions. This can often 
be prevented, however, by irrigation with salt solution immediately after 
the injection. 

As a dehydrating agent in adults, hypertonic glucose solution is used 
in a strength of 50 per cent, and in units of 50 or 100 c.c. In this amount 
and strength, it may be given intravenously every 2 hours for 3 or 4 
doses. It will have its maximum effect in from 15 to 30 minutes and will 
gradually cease to act during the next 2 hours. Its ill-judged or prolonged 
use will produce toxic dehydration. The addition of insulin to this therapy 
serves no useful purpose. 

Sterile magnesium sulphate solution may also be used intravenously 
as a dehydrating agent. Its use in this way, however, should be strictly 
reserved for those cases that have developed a rapidly advancing malig- 
nant edema of the brain. This is almost exclusively post-operative. This 
therapy puts an enormous extra load on the patient's circulation and, if 

Vol. VI. 339 



METHODS OF TREATMENT 135 

effective, produces a marked toxic dehydration which, in its turn, must be 
treated appropriately. Furthermore, any patient is liable to develop 
magnesium shock during the administration, and preparations must be 
made in advance to combat this emergency if, and when, it arises. A 2 
per cent, solution is used. It is made by dissolving the crystals in sterile 
distilled water. The dose for an adult is 100 c.c. of this solution, given 
into any convenient vein by the drop method. A skilled nurse or a physi- 
cian should be constantly in attendance. At least i hour should be used 
to give the single dose of 100 c.c. Before starting, a 10 c.c. ampoule of 
calcium chloride solution containing i gram of the salt (made by Lilly) 
and an appropriate syringe and needle must be at hand and prepared 
for immediate emergency use. If used, this calcium solution must be 
given slowly also. Both solutions must be kept entirely within the vein 
as any leakage into the surrounding tissues will produce a slough. Surgical 
shock, old age or a major circulatory disease are contra-indications to its use. 
Intramuscular Dehydration. — Dehydration may be produced in the 
new-born by the intramuscular injection of a sterile magnesium sulphate 
solution. This method is not ordinarily used in children or adults. A }/2 
c.c. of a sterile 50 per cent, solution may be given deeply into the muscles 
of the buttocks every 3 or 4 hours for no more than 4 doses. If the in- 
jection is made deeply enough, there is little danger of causing a slough. 

Blood Transfusion 

This is a much neglected and very useful procedure in the treatment 
of many varieties of cranio-cerebral injuries. In particular, such patients 
as have associated surgical shock, pre- and post-operative hemorrhage in 
addition to extradural bleeding and compound fractures, and a late secon- 
dary anemia, all benefit by this therapy. 

Surgical shock responds best to small transfusions of 100 to 250 c.c. 
each, repeated whenever the pulse pressure falls steadily or drops suddenly 
below 20 mm. of mercury. To replace lost blood, however, the amount 
transfused should be increased to from 250 to 500 c.c. at any one time. 

In the new-born transfusions are useful in the treatment of so-called 
or suspected hemorrhagic disease as well as for surgical shock. Here 
whole non-citrated blood is preferable. No typing or grouping of the 
blood is necessary during the first 10 days of life. The donor usually is 
either parent. Thirty to 60 c.c. commonly is given at each transfusion. 
Any vein other than the superior sagittal sinus may be used. The varia- 
ble position of the latter makes the liability of perforation and the forma- 
tion of an artificial subdural hematoma too likely for it to be safe. Pro- 

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136 CRANIOCEREBRAL INJURIES 

phylactic transfusions, as described, are a recognized adjuvant to the 
treatment of all types of cranio-cerebral injuries in the new-born. 

Operative Methods of Treatment 

No cranial surgery should ever be done outside of a hospital. No 
cranial surgery should ever be done in any hospital that is not properly 
equipped for this type of work. Obviously such surgery should be done 
only by one experienced in this form of surgical practice. A book intended 
for physicians, not surgeons, is not the place for descriptions of technique 
and procedures of operative surgical treatment. 

Non-operable Group of Cranio-cerebral Injuries 

Cranio-cerebral injuries can be divided into three groups. The first 
two are made up of the non-operable and operable cases respectively. The 
third group includes those cases in which the predominant symptoma- 
tolog>' is due to important complications of the local injury. The path- 
ology of the first group is such that treatment is non-operable, of the 
second such that treatment is operable and of the third group is such that, 
before instituting either operable or non-operable therapy, the associated 
complications must be corrected or else that, as the result of the treatment, 
usually operative, further necessary abnormal situations have been pro- 
duced that in their turn must be treated. This is a particularly useful 
method of classifying cranio-cerebral injuries, because it depends ulti- 
mately for its success on an understanding of the pathology present in 
any individual case. It is inevitable, therefore, that the treatment and 
consequently the mortality and morbidity will be improved. 

The non-operable group of cranio-cerebral injuries is made up of about 
63 per cent, of all such hospitalized patients. This 63 per cent, includes 
cases of concussion (i per cent.), edema and congestion (18 per cent.), 
and contusion (26 per cent.) and laceration (17 per cent.). These ratios 
probably are low for the first two and high for the last two because the 
drift of the severely injured patients is toward, and of the less severely 
injured ones away from, hospitals. It should be understood clearly that 
each succeeding diagnosis includes by implication the pathology that 
has been described under all preceding classifications. For example, 
although "concussion" completely describes the lesion that the patient 
is suffering from, "laceration" not only describes the predominant 
tearing of the surface of the brain but implies as well that contusion, 
edema and concussion are present also. This concept of the brain 

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NON-OPERABLE GROUP 136 (i) 

pathology is fundamental. The changes occur not only alone but also, in 
some form, as an accompaniment of the operable cases and of those classed 
under complications. Indeed, if this non-operable group is combined 
with the two commonest forms of operable cases, compound fractures and 
subdural hematomas, the combination will be found to include 92 per cent, 
of all cranio-cerebral injuries. 

Concussion 

Pathology. — The pathology of concussion is unknown. The best ac- 
ceptable explanation to date is based upon the predication that it is an 
example of an abnormal response to a vaso-vagal reflex. This dilates the 
arterioles of the brain, raises intracapillary pressure, lowers the general 
blood pressure and is associated with loss of consciousness. If conscious- 
ness returns before the chain of events has proceeded further, or if the 
patient's circulation is so efficient that further abnormal progress is pre- 
vented, he can properly be said to have suffered from concussion. In that 
case such a patient, on return to consciousness, will present absolutely no 
subjective or objective symptoms or signs of disease or injury to his brain. 
There may be a fracture of the bones of the skull or any other associated 
injury, but as far as the brain is concerned, neurological and mental ex- 
aminations, lumbar puncture and the like will be completely normal and 
remain so. 

Symptoms. — The symptom of concussion is loss of consciousness im- 
mediately following a blow on the head and followed by complete and 
permanent normality on recovery of consciousness again. Any variation 
from this sequence of events implies a more severe injury and a different 
diagnosis. 

Diagnosis. — The diagnosis is made on the history together with the 
total absence of any subjective symptoms or objective signs of injury to 
the brain other than unconsciousness. 

Treatment. — The disease, being self-limited by pathology and defini- 
tion and with complete normality synchronous with recovery of conscious- 
ness, requires no treatment. 

Mortality. — There is no mortality. 

Edema and Congestion 

These cases have as part of their pathology that described under con- 
cussion, and the diagnosis, to be complete and descriptive, should include 
this latter term. 

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136 (2) CRANIOCEREBRAL INJURIES 

Pathology. — Once the cerebral arterioles and capillaries have been 
dilated as the result of the vaso-vagal reflex, which has been predicated 
as the basic cause of concussion, a greater degree of injury or a less effi- 
cient circulation will either cause this process to advance or else fail to 
stop its further development. As a result, the capillaries leak, there is 
anoxia, an overdistention of the perivascular and perineuronals paces 
and a backing up and congestion of the venous circulation with decreased 
absorption of the cerebrospinal fluid and an overdistention of the ventri- 
cles. This is accompanied by a diminution of the size of the subarachnoid 
spaces. There is thus produced an increase in brain volume, intra- 
cortical congestion, petechial hemorrhages and radial thromboses and an 
increase in intracranial pressure due to a diminution of the water bed but 
with normal cerebrospinal fluid. 

Symptoms and Signs. — There is a history of a blow on the head suf- 
ficiently severe to produce unconsciousness. Following return to con- 
sciousness, such subjective symptoms as headache, dizziness, nausea, loss 
of memory and initiative and inability to concentrate appear. The intra- 
cranial pressure frequently will be elevated, but the cerebrospinal fluid 
always will be normal. Other objective signs may vary from a single 
cranial nerve palsy to hemiplegia with convulsions. 

Diagnosis. — The diagnosis is made from the history together with the 
cerebrospinal fluid findings as outlined above. 

Treatment. — - Treatment directed either toward shrinking the brain by 
dehydration or looking to removal, by lumbar drainage, of the excess 
backed up cerebrospinal fluid will be successful. Dehydration may be 
carried out by injecting hypertonic glucose solution intravenously or by 
the administration of magnesium sulphate by rectum. Their efficacy 
should be checked by the measurement of the intracranial pressure. With 
lumbar drainage enough cerebrospinal fluid should be removed at lumbar 
puncture to reduce an abnormally high pressure to normal levels. This 
procedure should be repeated every 24 hours until two successive normal 
pressure measurements have been obtained previous to the withdrawal of 
any cerebrospinal fluid. 

The amount of late disability that is caused primarily by earlier 
edema and congestion of the brain, or to any similar pathological state that 
is initiated by cerebral trauma is not known. It is influenced by the 
treatment that the patient received during both his acute illness and his 
convalescence. Other factors are his economic, social and intellectual 
backgrounds, his age and the state of his circulatory system. Any one or 
all of these may influence profoundly the occurrence of late symptoms, 
and mental deterioration and convulsive seizures are among the possible 

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NON-OPERABLE GROUP 136 (3) 

permanent after-effects. The patient's individual liability to any or all 
of these end results cannot be expressed in figures. 

Mortality. — The mortality should never exceed i per cent. The as- 
sociated presence of a non-operable injury to the bones of the skull alters 
neither the diagnosis nor the prognosis. 

Contusion and Laceration 

Cases of contusion and laceration, either separately or together, include 
as part of their pathology that described under edema and congestion as 
well as that under concussion. The diagnosis should be modified to suit, 
and it should become customary to include at least in it the words, 
edema and congestion. 

Pathology. ■ — If the cerebral pathology, as described above under both 
concussion and edema, is complicated by a bruise of the surface of the 
brain with a rupture of one or more cortical vessels, there is a contusion of 
the brain. If the injury has been severe enough actually to tear or lacer- 
ate the surface of the brain in addition, there is a laceration of the brain 
also. Contusions and lacerations of the brain merge into and overlap one 
another without any sharp distinction except in the extreme cases. Or- 
dinarily, any differentiation is a purely arbitrary personal one. Both are 
associated with concussion, edema and congestion and usually with sub- 
cortical hemorrhages as well. Both have free blood in the cerebrospinal 
fluid varying in amount from a few hundred cells in the mildest contusion 
to practically pure blood in the most severe laceration. Intracranial 
pressure is increased, first because of the edema and congestion and secon- 
darily, because of the mechanical blockade of the avenues of absorption of 
cerebrospinal fluid through the arachnoidal villi because of the free red 
blood cells therein. If this increase is marked, anemia and then edema 
of the medulla follow. Respiratory failure is associated with the latter 
and, when once present, usually proves to be inevitably fatal. 

Symptoms and Signs. — There is a history of a severe blow on the head 
followed by an unquestionable period of unconsciousness. This uncon- 
scious period may last for days and can be made to serve as a rough 
estimate of the severity of the brain injury. Loss of sphincter control 
may be associated with this coma, and, especially in the moribund cases, 
it is a common experience to find a generalized flaccidity with absent 
tendon reflexes. Respiratory irregularity, sudden fixed dilation of the 
pupils and a sudden increase in pulse rate and temperature occur just 
prior to death. If the injury has been less severe, the unconscious period 
will be followed by a varying degree of disorientation which is accom- 

VoL. VI. 339 



136 (4) CRANIO-CEREBRAL INJURIES 

panied often by active delirium. Nausea and vomiting are common. 
Headache and retrograde amnesia are almost invariable, and convulsions 
and any degree or kind of somatic or cranial nerve palsy can occur. 
Surgical shock invariably accompanies the more severely injured. The 
intracranial pressure is high provided the patient is neither dehydrated 
nor in surgical shock. The cerebrospinal fluid contains free blood in ac- 
cordance with the amount of damage to the surface of the brain. 

Diagnosis. — The diagnosis is made on the history together with the 
cerebrospinal fluid findings as outlined above. 

Treatment. — Treatment is most efficient when it consists of a judicious 
combination of dehydration and lumbar drainage. The dehydration will 
affect only the edema of the brain, however, and so must be supple- 
mented by a mechanical method such as lumbar drainage to counteract 
the eff^ects of the mechanical plugging of the openings in the arachnoidal 
villi. The technique is as described under "Edema and Congestion". 
Operative decompression as a therapeutic measure is contra-indicated. 
Exploratory trephination, however, is indicated and should be used as a 
diagnostic procedure whenever the patient fails to improve or gets worse 
after a suitable amount of non-operative treatment such as outlined 
above. (See also under Treatment of Edema and Congestion.) 

Mortality. — With proper diagnosis and under properly conceived and 
executed treatment the mortality for this group should never exceed i8 
per cent, and probably can be kept even lower. The presence of an as- 
sociated bone injury tends to decrease the patient's chances of survival, 
not because the break in the bone is, of itself, lethal, but because the blow 
that produced it must have been applied with greater force. 

Concussion, edema and contusion or laceration or any combination 
of them may or may not be associated with any of the specialized forms 
of cranial bone injury, with any type of meningeal hemorrhage and hence 
with any of the operable group of cases or those whose presenting symp- 
toms place them among the complications. All of these latter conditions, 
however, will be characterized by their own additional pathological pecu- 
liarities and, therefore, must be considered as separate diagnostic and, 
therefore, therapeutic entities. 

The Operable Group of Cranio-cerebral Injuries 

The second great group of cranio-cerebral injuries is that whose pre- 
dominant pathology is such that therapy must include operative measures 
on the cranium. It must be understood clearly, however, that although 
the predominant pathology is of this particular type, it nevertheless over- 

VoL. VI. 339 



SUBDURAL HEMORRHAGE 136 (5) 

lies and is present in addition to the fundamental cerebral pathology that 
has been described in the previous section. It is also subject to the com- 
plications that are enumerated in the succeeding section. 

This operable group of cases includes about 37 per cent, of all hospi- 
talized cranio-cerebral injuries. It is made up of sub- and extra-dural 
hemorrhages and compound and depressed fractures of the skull. The 
lesions themselves may be expanding, non-expanding or a combination of 
both in that order. Consequently, the intracranial pressures may range 
from high levels to normal figures. Both levels may be present in any 
one case, and yet the lesion be treatable only by operative interference. 
The group mortality is at present about 32 per cent. As we become more 
willing to operate earlier and as our operative technique improves, 
however, this figure should be lowered. In general, treatment must be 
such as will care properly for the underlying cerebral pathology and 
in addition avert sepsis, control otherwise fatal hemorrhage and obviate 
later complications without undue risk to the patient. Ordinary diag- 
nostic methods should be supplemented without hesitation by bilateral 
exploratory trephination. Subdural hematomas occur most frequently (18 
per cent.) with a mortality of 36 per cent. Next are the compound frac- 
tures (11 per cent.) with a mortality of 31 per cent, and permissible sepsis 
of not over 5 per cent. Depressed fractures are next (4}/^ per cent.) with 
a mortality of 5 per cent., which should be under i per cent., and finally 
the extradural hematomas (3 per cent.) with a mortality of 55 per cent. 

Subdural Hemorrhage 

This practically always is associated, whenever due to a blow on the 
head, with one of the forms of cerebral pathology described in the preced- 
ing section. The exception occurs in connection with trivial injuries, 
which do not even produce a concussion, but which do rupture a bridging 
vein as it crosses the subdural space. Subdural hematomas also develop 
in the absence of injury and in association with scurvy, as an extension 
from a subarachnoid hemorrhage which originated in cerebral vascular 
disease, or in connection with cerebral tumors and other analogous condi- 
tions. Except as the end stage of an acute event, which follows local in- 
jury, there are no "chronic" subdural hematomas. The fact that the clot 
was discovered and treated an appreciable time, sometimes years, after it 
had been caused originally by a partly forgotten accident does not justify 
its segregation into a separate class. In a series of over 200 verified sub- 
dural hematomas 35 or ii.i per cent, have been present on both sides of 
the cerebrum and 7 or 3.2 per cent, have recurred after operation. 

Vol. VI. 339 



136 (6) CRANIOCEREBRAL INJURIES 

Pathology. — Subdural hematomas are of three types which merge into 
one another and vary in their development with the passage of time. In 
their pure form they are either solid, mixed or fluid. The consistency of 
any given clot depends upon the original relationship between the solid 
and fluid elements of the contents of the subdural space. They all begin 
in response to the rupture of a blood vessel and the escape of its contents 
into that space. With all except the solid ones there is an additional tear 
of the arachnoid and the escape of a varying amount of cerebrospinal fluid 
into the same subdural space. In any case, whether made of up a pure 
solid clot or of a majority of transplanted cerebrospinal fluid to which has 
been added a minimum of clot or fluid blood, the resultant hematoma is 
incarcerated in its new position and can be removed only by surgery. If 
not so removed, the solid clots organize and become either thick walled 
cysts with small amounts of liquified blood clot in their centre and possible 
flakes of calcium in their walls or a membraneous sheet of tissue either 
lying between the arachnoid and dura or added and attached to the latter 
which thus is thickened locally. The mixed and fluid types end up as a 
collection of fluid with a protein content slightly higher than that of the 
cerebrospinal fluid. They move about freely in the cranial subdural space, 
shifting with each change in position of the patient's head, and remain 
permanently unabsorbed. 

The solid clots are expansile only during the time of active bleeding. 
Thereafter, their effect upon intracranial pressure depends upon their size 
and the resultant compression of the brain and interference with the ab- 
sorption of the cerebrospinal fluid. Their organization takes place only 
by the extension of fibroblasts from the under side of the dura over both 
surfaces of the clot. As this proceeds, an outer membrane, next to the 
dura, and an inner membrane, next to the arachnoid, are formed and 
sooner or later enclose the entire clot. If the clot is small, this process 
of organization from the periphery toward the centre will take place more 
rapidly than the liquefaction of the enclosed blood. This will produce a 
solid membrane, which lies as a sheet beneath the dura or is attached to 
and an integral part of that structure. If the organization is so slow, due 
to the size of the clot, that blood in the centre of the hematoma is lique- 
fied, a thick-walled cyst containing a concentrated solution of protein will 
result. The only further change will be the deposition of calcium in the 
walls of this cyst. The rate of the organization of these solid clots is re- 
markably constant. As a result a microscopic study of a section of dura 
and adjoining membrane and clot will enable one to predict its age and, 
therefore, the time of the causative injury, with considerable accuracy 
up to three months. As can be appreciated readily, this might have con- 

VoL. VI. 339 



SUBDURAL HEMORRHAGE 136 (7) 

siderable importance from a medico-legal aspect. The solid hematomas 
usually are located over the cerebrum but may occur over the cerebellum. 

The mixed clots, being made up of both solid clots and a solution of 
blood in cerebrospinal fluid, are not only expansile during the actual ac- 
tive bleeding but also later by virtue of the protein content of the liquid 
part. This is necessarily high and becomes higher as more and more 
blood goes into solution. The fluid hematoma is separated from the 
cerebrospinal fluid, a solution with a low concentration of protein, by the 
arachnoid. The arachnoid acts as a dialyzing membrane and promotes 
the exchange of fluid and electrolytes from the low to the higher concen- 
trate in accordance with well known physico-chemical laws. As a result 
the fluid hematoma constantly is being increased in bulk. This increase 
goes on rapidly until after the free blood has been dissolved and the solid 
clots have been organized; then more slowly until the protein content of 
the subdural space approximates that of the cerebrospinal fluid. The 
period of rapid expansion reaches its peak about 21 days after the accident 
and is continued during the following 14 days. Thus, for about 5 weeks, 
the mixed hematomas are expansile lesions and may be expected to have 
an increase in intracranial pressure as an accompaniment. A static end 
point in dilution is not reached for another 2 months, but the rate of 
dilution during this period is so slow and the adjustments of the brain to 
the widely spread out subdural fluid so adequate that the intracranial 
pressure remains unchanged at normal. Mixed hematomas occur only in 
the cerebral subdural space and usually as a single collection of fluid 
which moves freely about the entire space. Occasionally, there may be 
two separate fluid collections, one on either side of the cerebrum, with 
different chemical contents. It has not been determined what the mech- 
anism is that keeps them separate and distinct. 

Fluid he?natomas contain no gross blood clots. They originate as a 
solution of a minimal amount of blood in a maximal amount of cerebro- 
spinal fluid. For the reasons given under mixed clots they too are expan- 
sile for a period of ten days with a peak on the sixth day. Thereafter, 
they are static, and their protein content approximates that of cerebro- 
spinal fluid. At this time this hematoma and the end stage of the mixed 
hematoma are indistinguishable. The average protein content of these 
two types of fluid ranges from a high of between 200 and 300 mgm. 
per cent, to a low of 75 mgm. per cent. Suspected fluid that is 
thought to have been removed from the cerebral subdural space after a 
cranio-cerebral injury, and that after being properly analyzed and cor- 
rected has a total protein of 100 mgm. per cent, or over, can be classed 
as subdural fluid. Fluids with lower protein, however, cannot be differ- 

VoL. VI. 339 



136 (8) CRANIOCEREBRAL INJURIES 

entiated certainly from subarachnoid fluid on the chemical evidence alone. 
Subdural fluid hematomas, whether originally mixed or fluid in type, have 
been shown to be present in the static end stage as long as six years after 
injury and possibly longer. Invariably they have been cerebral in location. 

Symptoms. — The symptoms of the large majority of subdural hem- 
atomas are those of the associated brain injury. There will be a his- 
tory of a blow on the head followed by unconsciousness and usually 
headache as well as all the rest of the variable symptomatology as- 
sociated with fundamental brain pathology. In those few that de- 
velop because of the rupture of a bridging vein after a trivial or no 
known injury to the head, there is often, but not necessarily always, a 
late development of symptoms. This follows a period of normality which 
has intervened between the actual rupture and the onset of the patient's 
complaints. In the older cases patients frequently will complain of re- 
current waves of symptoms during which they have an indefinite, listless 
type of inertia or lack of initiative and possibly, associated mild headaches 
and dizzy feelings in the intervals. 

Signs. — The signs are those of whatever associated brain injury may 
be present. A manic type of delusional restlessness is common, although 
stuporous patients tend to become more and more deeply comatose. All 
varieties of reflex changes and peripheral paralyses have been demon- 
strated. Unilateral facial palsy of the central type is an unusually fre- 
quent finding. Fixed dilation of one pupil, usually without demonstrable 
ptosis of the upper eyelid, occurs as frequently on the side opposite to, as 
on the same side as, the hematoma. The cerebrospinal fluid usually will 
have the characteristics given it by the associated brain injury. Its pres- 
sure will be high, while the clots are expansile or in the presence of large 
solid clots, but otherwise it will be normal. Surgical shock and dehydra- 
tion will cause lowering of the high pressures, but the presence of a sub- 
dural hematoma can not be ruled out by the failure to demonstrate a high 
pressure even in their absence. 

Diagnosis. — Because of the variability and unreliability of the signs 
and symptoms of all types of subdural hematomas the diagnosis is made 
finally by a trans-temporal exploratory trephinement. Ordinarily this 
should be bilateral. It is indicated whenever in acute cases, and after 
surgical shock and dehydration have been ruled out, a patient fails to 
improve or gets worse under properly applied non -operative therapy. In 
the older cases it is permissible, whenever the patient will consent to 
undergo the procedure in spite of the expressed assurance of the surgeon 
that it is quite as likely to prove to be a completely useless therapeutic 
procedure as it is to be of any help. Encephalography and electroenceph- 

VoL. VI. 339 



COMPOUND FRACTURES 136 (9) 

alography will be of assistance only in an insignificant number of solid 
clots and are entirely useless when the lesion is fluid in type. 

Treatment. — The treatment of all types and ages of subdural hema- 
tomas is exclusively operative. The preferred technique is by means of 
a trans-temporal procedure. Bone-flap operations except in the old solid 
clots and irrigation of the subdural space between trephine holes are 
contra-indicated. The clot should be removed completely, if fresh, and 
the subdural space drained for 48 hours. If old and solid, the outer mem- 
brane should be opened widely and as much of it and the inner membrane 
removed as is safe. It does no harm to leave large sections of both behind 
provided the cavity is emptied and drained for 48 hours. Specimens of 
the dura and membranes and of the subdural fluid should be taken in- 
variably and examined histologically and chemically respectively. (See also 
under Treatment of Edema and Congestion.) 

In the less recent cases there is an added element of excessively dam- 
aged morale that has to be dealt with. These patients have been told so 
often by so many authorities that their symptoms are either non-existent 
or hysteroid that they have, of necessity, become skeptical about assur- 
ances of cure, no matter who gives them. In addition to removing their 
hematoma and thus relieving them of their symptoms, the surgeon has to 
combat this attitude. Furthermore, they have, in most instances, been 
forced to develop the habit of invalidism. This has been their only means 
of self -justification. Even with the best intentions and the greatest co- 
operation this is a hard habit to break. Their convalescence is liable 
to be prolonged and to require much sympathetic assistance on the part 
of the surgeon. 

Mortality. — The mortality of this group at this time is about 35 per 
cent. This doubtless can be reduced as the diagnoses are made earlier 
and operative technique becomes more perfect. 

Compound Fractures of the Skull 

Compound fractures of the skull are first of all a problem in sepsis or 
at least potential sepsis and secondly a problem in the treatment of what- 
ever underlying brain injury is present, or whatever complication exists 
by virtue of the location of the fracture. The fracture may be linear, 
comminuted or depressed. It may involve venous sinuses or paranasal 
air sinuses; the brain injury may be mild or severe, but in any and every 
instance the case remains one that is at the time, or is going to be within 
48 hours, infected. All other considerations of diagnosis and treatment 
fade into insignificance in the light of this one fact. 
Vol. VI. 339 



136 (lo) CRANIO-CEREBRAL INJURIES 

Pathology. — The pathology is partly that of the fundamental associ- 
ated brain injury as described in a previous section. In addition there is 
an open infected wound which at the very least involves the outer table 
of a skull bone and at the very most the subcortical tissue and the blood 
stream. In this wound is a culture medium of bruised necrotic tissue 
mixed with blood clot and inoculated with or contaminated by bacteria. 
These have been introduced by the compounding agent. Foreign bodies 
such as dirt, stones, glass, bullets, pieces of head-gear and fragments of 
bone may be included as well. If the fracture line enters the wall of a 
paranasal air sinus, and if the mucous membrane of that sinus is torn in 
addition, there is opened up an extra source for infection of the meninges 
and brain by direct extension from the nose. If the cribriform plate is 
included, the same holds true to a greater degree. Thus there is associ- 
ated with every compound fracture of the skull a potential meningitis, 
encephalitis or cortical abscess. If the bacteria that are contaminating 
the wound are virulent hemolytic streptococci or pneumococci, at least 
meningitis is an actuality from the time of inoculation. If the infecting 
agent belongs to the more common but less virulent staphylococcic group, 
its radial spread beyond the confines of the damaged tissues is less rapid. 
The actual rate of this spread, whether measured in distance or time, 
cannot be determined. This is because of variables that come from at- 
tempting to estimate among other things the degree of blockade of the 
lymph and blood vessels produced because of mechanical compression 
from the impact of the compounding agent, the virulence of the bacteria, 
the resistance of the patient, the manipulation and unintentional massage 
of the infected tissues during so-called cleaning or sterilization procedures 
and the suitability of the media. Experience has demonstrated, however, 
that, with the exception of cases infected by hemolytic streptococci and 
pneumococci, significant radial spread of bacteria to surrounding, previ- 
ously uninvolved tissues does not take place for 48 hours from the time of 
implantation, provided the wound is not manipulated. In the later stages 
foreign bodies besides being harborers of bacteria themselves will pro- 
duce the tissue changes characteristic of the "foreign-body reaction" with 
its inflammation and even liquefaction with necrosis of adjacent re- 
gions. 

Symptoms and Signs. — The symptoms are those of the associated 
brain lesion. The fracture itself produces no symptoms. The signs are 
those characteristic of a lacerated wound of the scalp and underlying 
tissues including the pericranium. This wound will overlie all or part of a 
fracture line that may be limited to the outer table only or may involve 
the whole thickness of the bone with comminution or depression of the 

Vol. VI. 339 



COMPOUND FRACTURES 136(11) 

fragments. In the latter case the meninges may be torn and the surface 
of the underlying brain lacerated. Brain tissue may be lying on the scalp 
adjacent to the wound. There may be bleeding from the nose and mouth 
and perhaps a cerebrospinal rhinorrhea, if the paranasal air sinuses or the 
cribriform plate have been included in the fracture line. If the compound- 
ing has been caused by a bullet, it and fragments from it will be visible 
by x-ray unless it has passed through the cranium. In this latter case 
the compounding will be double. In addition any signs that ordinarily 
might be produced by surgical shock, dehydration, profuse hemorrhage 
or any form of brain, meningeal or cranial nerve injury will be present. 
This will include the characteristic cerebrospinal fluid changes. 

Diagnosis. — The diagnosis can be made accurately only by palpation 
through the scalp wound with the examiner's sterile finger. To do this, 
it is proper to remove previously placed stitches or to enlarge the scalp 
wound. Adequate time should be taken to be sure of the condition at the 
first palpation, and thereafter no further manipulation of the wound by 
anyone should be permitted until the surgeon is prepared to follow it up, 
if necessary, by a formal debridement. Intact pericranium over the frac- 
ture line, no matter what the condition of the scalp, prevents compound- 
ing. X-ray examination, except to determine the presence of a foreign 
body such as a bullet or to demonstrate the involvement of the walls of 
a paranasal sinus in the fracture line, is needless and confusing. The 
presence or absence of surgical shock should be ascertained, and the de- 
gree and type of cerebral injury should be determined by appropriate tests 
as part of the preoperative diagnosis. 

Treatment. — Once the diagnosis is made, therapy is exclusively surgi- 
cal. It consists of debridem.ent with appropriate modifications within 48 
hours of the time of the receipt of the accident. The physician, however, 
has the definite responsibility of seeing to it that no one makes any at- 
tempt of any kind to clean or otherwise touch the scalp wound prior to 
the start of the major surgical procedure. The preoperative dressing 
should be dry sterile gauze held in place by a bandage and put there im- 
mediately after the palpation that has made the diagnosis. Specifically, 
no irrigation, no shaving of the scalp, no removal of dirt or pieces of bone 
or any similar manipulative procedure should be permitted. The impor- 
tance of this cannot be overestimated. Surgical shock and the underlying 
associated brain pathology should be treated as outlined in a previous 
section. If the preoperative treatment is as outlined, the debridement 
100 per cent, and done sufficiently soon, and the fracture does not involve 
a paranasal sinus, the cribriform plate or the supra-orbital ridge, the oper- 
ative wound can be closed without drainage and should heal by first in- 

VoL. VI. 339 



136 (12) CRANIO-CEREBRAL INJURIES 

tention. Sepsis should not develop in more than 5 per cent, of the cases. 
Whenever culture from the wound shows hemolytic streptococci or pneu- 
mococci, sulphanilamide should be given at once in sufficient quantity to 
produce and keep a 10 mgm. per cent, concentration in the blood of the 
patient. Appropriate antipneumococcic serum should be administered 
also when indicated. In all cases of compound fracture into the frontal 
or ethmoid sinuses or associated with cerebrospinal rhinorrhea the ad- 
ministration of sulphanilamide should be started at once following the 
admission of the patient to the hospital and without waiting for cultures 
from the wound or nose. Whenever sulphanilamide is used, careful daily 
observations on the white and red blood cell counts should be made to 
forestall an unexpected development of agranulocytosis or hemolytic ane- 
mia. Careful observation for other toxic phenomena should be made, too. 
(See also under Treatment of Edema and Congestion.) 

Permissible sepsis of any type following compound fracture of the skull 
should not exceed 5 per cent. This probably can be lowered somewhat 
as soon as the use of sulphanilamide becomes more widespread and better 
understood. The significance of this figure can be appreciated, when it is 
realized that actual analysis of cases of compound fracture of the skull 
treated by so-called "general surgical methods" shows an incidence of 
infection of 75 per cent. 

Mortality. — The mortality from compound fracture of the skull 
should not exceed 23 and should be 20 per cent. Widely accepted figures 
are over 30 and in many instances over 50 per cent. 

Extradural Hemorrhage 

Extradural hematomas have served commonly as the typical prototype 
of all cranio-cerebral injuries. This is now known to be entirely incorrect. 
Furthermore, it is no longer possible to limit this diagnosis to those cases 
which have the classical pathognomonic history. As a result, and since 
the mortality of these cases rises in direct relationship to the length of 
time they go undiagnosed, it has been necessary to include them in the 
group of operable cases in whom the final diagnosis may well rest on an 
exploratory trephination. 

Pathology. — Extradural hematomas practically always are expanding 
lesions with a constantly growing blood clot which lies between the skull 
and the dura. The source of the clot is found in the rupture of any part 
of the middle meningeal artery or one of the large cranial venous sinuses. 
The clots commonly are unilateral and cerebral, although they may occur 
simultaneously on both sides of the cerebrum or singly over the cere- 

VoL. VI. 339 



EXTRADURAL HEMORRHAGE 136 (13) 

bellum. They are always associated at the time of the original injury 
with some one of the forms of fundamental brain pathology. 

Symptoms. — In the classical case the symptoms are pathognomonic. 
The history has three distinct parts. Following the blow on the head, 
the patient is knocked unconscious, and the artery or sinus ruptured. 
This primary period of unconsciousness is due to the associated funda- 
mental brain pathology and lasts in point of time in accordance with the 
degree of severity of that pathology. If it be only concussion, the pri- 
mary loss of consciousness may be no more than momentary and its 
presence unknown to the patient or the witnesses and undemonstrable 
by the physician. If it be due to a lacerated brain, however, the uncon- 
sciousness may last for days and extend long past the second stage of the 
pathognomonic history which is the stage of consciousness. Thus, the 
ability to recognize this second period depends on the degree of funda- 
mental brain injury. Whether it is recognizable or not, however, it is 
during this time that the clot is being formed between the skull and the 
dura. It will be seen that this period must end when the extradural clot 
is big enough to produce unconsciousness on its own account. The length 
of this second period therefore will depend on the degree of adhesiveness 
between the dura and the inner surface of the bone. If it is slight or ab- 
sent and the bleeding arterial, an enormous clot may be formed in a half 
hour or less. On the other hand, if the two structures are firmly attached 
to one another, a clot large enough to deform the cerebrum sufficiently to 
produce coma may take days to form and may be made up of several 
successive hemorrhages. Regardless of the length of time it lasts, how- 
ever, and whether or not its presence is masked completely by the asso- 
ciated cerebral injury, this second period is succeeded by a third period 
of slowly increasing unconsciousness. This is due to the coma following 
dislocation and compression of the cerebrum by the growing clot. It is 
recognizable as a third period only if preceded by the typical second pe- 
riod of consciousness. This third period ends with the death of the 
patient, if no relief is provided. 

Signs. — All the signs that are present as the result of any type of 
non-operable brain injury may be present in any patient with an extra- 
dural hemorrhage. In addition during the second period there may be 
complaint of headache and difficulty with speech. During the third period 
there may be paralysis, either ipsi- or contra-lateral, convulsions, aphasia, 
possibly a facial palsy, dilatation and fixation of one pupil and increased, 
absent or abnormal reflexes. X-ray data are essential in doubtful cases. 
If the film shows a fracture line which crosses the groove of the middle 
meningeal artery or a large venous sinus, the suspected presence of an 

Vol. VI. 339 



136 (i4) CRANIOCEREBRAL INJURIES 

extradural clot will be verified sufficiently to justify operation. The film 
is valueless of course, unless both the fracture line and the grooves are 
visible. The intracranial pressure always will be high even in the presence 
of surgical shock or dehydration. The cerebrospinal fluid may or may not 
be bloody depending on whether there has been an associated contusion 
or laceration of the brain. 

Diagnosis. — In the classical case the diagnosis is made from the his- 
tory. Such instances are rare. In the ordinary case the diagnosis is 
presumed from the history, the physical findings, the x-ray film and by 
the failure of the patient to get better under properly applied non-opera- 
tive therapy and is confirmed by prompt transtemporal exploratory tre- 
phination. 

Treatment. — This is surgical. A sub-temporal decompression should 
be provided at the earliest possible moment, the clot completely removed and 
the bleeding point closed. Transfusion for loss of blood almost certainly 
will prove necessary during, and possibly before and after the opera- 
tion. The associated brain injury is treated in accordance with the diag- 
nostic needs. The loss of bone in the temporal region is of no consequence 
provided the attachments of the temporal muscle have been left intact 
at the time of operation. This muscle provides adequate protection 
against usual injuries. (See also under Treatment of Edema and Conges- 
tion.) 

Mortality. — Extradural hematomas have, in spite of the best and 
earliest treatment, far and away the highest mortality of all cranio- 
cerebral injuries. The rate is 55 per cent, and is exceeded only by that 
of complicating meningitis. 

Depressed Fractures of the Skull 

The diagnosis of depressed fracture of the skull should be limited to 
those cases in which there is no complicating additional scalp, bone, air- 
sinus or meningeal injury. Associated cerebral injury will be present al- 
ways and may be of any of the non-operable varieties. 

Pathology. — The pathology is that of a fracture of one of the bones of 
the skull which has been, in whole or in part, moved inward in such a 
way as to invade the cavity of the cranium. It varies from the "celluloid 
ball", spoon-shaped dent in the infant's skull to the immovable locked 
fragmented depression of the adult. The latter may be linear or commi- 
nuted and the fragments may be flat or on edge and may involve both 
tables or the inner table only. Any one of the cranial venous sinuses may 
be torn by the lacerating fragment as may the dura or the surface of the 

Vol. VI. 339 



LACERATED WOUNDS 136 (15) 

brain. Old fractures tend to unite in an unreduced position and may 
produce rounded tumors that stick down into the cranial cavity and make 
local pressure on the underlying dura and cortex. At times, however, a 
depressed fracture will heal in such a way as to leave no depression and 
the inner surface of the bone smooth and flat. 

Symptoms and Signs. — The symptoms are those of the associated 
brain injury. There is usually a sub-peri cranial or sub-galeal hematoma. 
It is characteristic of the former to develop what appears to be a hard 
raised edge in relation to the softer centre, whether there is a bony de- 
pression present or not. Diagnosis of this kind of fracture by palpation, 
therefore, is notoriously inaccurate. The cerebrospinal fluid findings will 
be those of the associated brain injury. X-ray usually will demonstrate 
the depression but occasionally may give a false impression and lead one 
to diagnose a depression when there is none present or vice versa. 

Diagnosis. — The diagnosis of the bony lesion is made only by x-ray. 
The diagnosis of the associated cerebral damage is made as described in 
the previous sections. 

Treatment. — The treatment is surgical and is carried out by lifting 
the fragments with as little associated removal of the damaged bone as is 
consistent with complete elevation. All depressed fractures except those 
in the region of the foramen magnum must be elevated. However, no 
elevation should be attempted until after the intracranial pressure has 
been reduced to, and fixed again at, a normal level by appropriate therapy 
of the associated brain injury. Because of the cerebral venous congestion 
it is only in this way that a possible death on the table from operative 
hemorrhage or air embolus can be avoided. If the fracture is not elevated, 
the liability of later convulsive seizures, headache and indefinite disabling 
symptoms is increased. (See also under Treatment of Edema and Conges- 
tion.) 

Mortality. — The mortality rate certainly should not exceed 5 per cent, 
and, if the cases are handled properly, ought to be zero. 

Lacerated Wounds, Avulsion and Hematomas of the Scalp 

Lacerated Wounds of the Scalp. — Most such wounds are primarily 
infected. All have an associated galeal hematoma. Many contain foreign 
bodies. The treatment, therefore, is surgical. The preferred method is by 
debridement and primary suture in two layers with interrupted #7 silk 
stitches and without drainage. Next in order of preference is a cleansing 
with soap and water, alcohol, ether and i per cent, alcoholic solution of 
iodine, no suture at all and dressings of gauze soaked in sterile boric oint- 

VoL. VI. 339 



136 (i6) CRANIO-CEREBRAL INJURIES 

merit. If stitches are put in, they should be loose, far apart and through 
and through; drainage with rubber tissue or strands of silk-worm gut 
should be used for 48 hours. Flamed adhesive plaster may be used in 
place of the stitches. Under no condition of extent or location should a 
lacerated wound of the scalp be sewn tightly or without drainage unless 
an adequate debridement has first been performed properly. 

Avulsion of the Scalp. — The type of treatment suitable for avulsion 
of the scalp depends primarily upon the blood supply of the avulsed por- 
tion. All tissue that is viable should be debrided, replaced and sutured 
loosely. Dead portions should be sacrificed at once. The operation 
should be done under a general anaesthetic and in a hospital. Mechanical 
antisepsis is used and supplemented by i per cent, alcoholic solution of 
iodine. A stronger solution cannot be used safely. If large areas of bone 
have been left bare, multiple perforations through the outer table into the 
diploe should be made at once. Drainage under the flaps must be pro- 
vided for 24 hours, and multiple scarification of the scalp near all suture 
lines should be practised. Dressings should be kept constantly moist 
with warm salt solution for 3 or 4 days. Skin grafting may be resorted to 
later, if necessary. The end results always are much better than the orig- 
inal condition would lead the surgeon to expect. 

Subperiosteal Hematomas and Cephalhematomas of the New-Born. — 
These two types of hematomas of the scalp should be left scrupulously 
alone, if the scalp over them is intact. Both of them are completely out- 
side of the bone, are limited by the suture lines and will absorb, if not in- 
fected. There is no good evidence to show that their presence causes any 
intracranial abnormalities. 



Complications of Cran o-Cerebral Injuries 

The complications of cranio-cerebral injuries fall into four great classes. 
The first covers associated bodily conditions and includes surgical shock 
and dehydration. The second group is made up of conditions that are 
associated with infection in the cranial cavity. The third consists of non- 
specific linear fractures of the base and vault of the skull and lesions 
caused by them, and the fourth covers those conditions that arise as com- 
plications out of necessary previous therapy. 

While the physician must, of necessity, have a speaking acquaintance 
with all complications, his most intimate association will be with those 
arising out of general bodily conditions, that is, surgical shock and de- 
hydration. The others may be looked upon as problems in surgical rather 
than medical therapy, and once the physician recognizes their presence and 

Vol. VI. 339 



SURGICAL SHOCK 136 (17) 

knows what to expect of surgical therapy, he need not concern himself 
further about them. 



Complications Due to Associated General Bodily Conditions 
Surgical Shock 

Surgical shock, when present, is one of the most important of the 
complications associated with cranio-cerebral injuries. It is either an 
actual or potential accompaniment of all the major ones. It differs in no 
way from the surgical shock that is seen in other major injuries except 
for an increased preponderance of coma. 

Pathology. — The pathology is in dispute, but the best evidence to 
date is in support of Cannon's theories. Briefly, according to him, a 
condition is set up in which there is leakage of blood serum or any elec- 
trolyte from the capillaries into the tissue fluids. This reverses the ordi- 
nary osmotic relationships between the intra-capillary and extra-capillary 
fluids, leads to increased viscosity of the circulating blood, an alteration 
of the relationship between blood cells and serum, tissue anoxia and 
edema, decreased systolic and pulse pressure, pallor, sweating and collapse. 

Symptoms and Signs. — The symptoms of surgical shock include a 
history of a major injury which, if it has been to the head, is associated 
with unconsciousness and on return of consciousness with moderate 
disorientation and apprehension. The presence of shock usually is char- 
acterized by a falling systolic or persistently low pulse pressure, pallor, cy- 
anosis, sw^eating, subnormal temperature, high pulse and rapid respiratory 
rate. If the patient is unconscious, often there will be absent reflexes and 
relaxed sphincters. The cerebrospinal fluid pressure, except in cases of 
massive brain injury, will be below normal and may be zero. The fluid 
usually is bloody because of the associated contusion or laceration of the 
brain. 

Diagnosis. — The diagnosis should be made provisionally in the pres- 
ence of any severe cranio-cerebral injury and is confirmed by blood 
pressure, pulse and temperature readings and, if necessary, by the meas- 
urement of the cerebrospinal fluid pressure. 

Treatment. — The best treatment is to administer repeated small trans- 
fusions of properly matched citrated or whole blood. One hundred and 
twenty-five to two hundred and fifty c.c. may be given at each transfu- 
sion. There should be also an absolute prohibition of any and all diag- 
nostic or other therapeutic procedures until after the pulse pressure has 
returned to normal. When compatible blood is not available at once, and 
Vol. VI. 339 



136 (i8) CRANIO-CEREBRAL INJURIES 

it usually is not, a 50 per cent, solution of glucose, if given intravenously 
in doses of 100 c.c. at a time for adults, is a satisfactory substitute until 
a donor can be obtained. An even more satisfactory substitute is a solu- 
tion of pure acacia. This, however, generally is not available in a form 
that can be safely used in an emergency. Normal salt-solution and adren- 
alin are contra-indicated as methods of treatment for surgical shock. The 
first, being a solution of electrolytes, leaks from the capillaries almost as 
fast as it is put into the circulating blood and thus increases tissue 
anoxemia and edema. The second increases the resistance of the periph- 
eral circulation and thus reduces still further the already inadequate sup- 
ply of oxygen-bearing blood to the cells, and as a result, tissue anoxemia 
and cellular damage are increased. Solutions of glucose and acacia are 
useful because the large size of their molecule retards their escape from 
the leaky capillaries, and they can thus serve to increase the volume of 
circulating blood. Normal blood is useful, because it provides a mechan- 
ism whereby the oxygen -carrying capacity as well as the volume of the 
circulating blood is increased. Phenolbarbital (luminal), by mouth, in 
small doses, and caffeine sodium benzoate intravenously may be of aid. In 
addition the customary general therapeutic measures must be used. 
No figures are available as to the rates of occurrence or mortality. 

Toxic Dehydration 

Toxic dehydration is one of the commonest but most universally un- 
recognized complications of cranio-cerebral injuries. There is no test 
which will demonstrate accurately its presence or absence, and the diag- 
nosis has to be made on clinical evidence only. 

Pathology. — The pathology is that associated with an imbalance of 
the water metabolism of the body. Acidosis may be present in severe cases. 

Symptoms and Signs. — There is a history of a blow on the head and 
a period of unconsciousness either from 3 to 4 or from 10 to 14 days 
previously. If the patient has regained consciousness previously, there is 
increasing stupor. In the variety that develops early, usually there has 
been vomiting, profuse sweating, overheating from any cause and an in- 
tentional or accidental limitation of fluid intake especially in unconscious 
patients. Thus, the latter has been associated with a major but unnoticed 
and uncompensated fluid loss. In the late variety the history usually will 
reveal an over-dosage of either hypertonic solutions intravenously or of 
magnesium sulphate solution by rectum. Their original use may have had 
a therapeutic justification, but that no longer exists. Often there will be 
a history of ether or barbiturate anesthesia and possibly an operation as 

Vol. VI. 339 



MENINGITIS 136 (19) 

a starting point. Both types usually will show a rising temperature, a 
major discrepancy between the amounts of fluid intake and output as 
charted graphically, a subnormal intracranial pressure which may be 
zero and in the more serious instances, acetonuria and a decrease in 
the carbon dioxide combining power of the blood. The latter is particu- 
larly apt to develop in young children from what would appear to be in- 
adequate reasons. 

Treatment. — Treatment consists of the administration at all times of 
sufficient fluid to prevent dehydration. In adults this requires under 
ordinary circumstances the ingestion or absorption into the body by other 
means of at least 3,500 c.c. for each 24-hour period. If toxic dehydration 
develops, this fluid intake must be stepped up to between 5,000 and 6,000 
c.c. in each 24-hour period. Appropriate adjustments in intake must be 
made in children, chronic cardiacs and in patients that develop edema 
of the extremities or lungs from any cause. Fluid is given preferably by 
mouth but can be given by hypodermoclysis or through an inlying stom- 
ach tube. 

Ratio of Occurrence. — This condition occurs in about 2.6 per cent, of 
hospitalized patients with cranio-cerebral injuries. 

Mortality. — It is not necessarily a serious or fatal complication, but 
it may prove to be so if unrecognized or if allowed to progress without 
treatment. The mortality among hospitalized patients is 20 per cent. 

Complications Due to Infection in the Cranium and Cranial Cavity 

Regardless of the type of treatment used, a certain amount of infection 
is inevitable in any significant group of surgical cases. In cranio-cerebral 
injuries it commonly takes the form of meningitis, brain abscess, osteo- 
myelitis or an infected scalp wound. The incidence of infection in a hos- 
pitalized group of over 1,200 such cases, whether of the operable or 
non-operable type, was about 3 per cent, and the mortality 51 per cent. 
Two and one-tenth per cent, of this infection was considered to be unjusti- 
fiable. Practically all of these latter followed operative interference. Of 
the remaining 0.9 per cent, a little more than half were in the non- 
operable group. 

Meningitis 

Meningitis in association with a cranio-cerebral injury most commonly 
is caused by the staphylococcus, next by the streptococcus and less often 
by the pneumococcus and influenza bacillus. 

Vol. VI. 339 



136 (2o) CRANIOCEREBRAL INJURIES 

Pathology. — The pathology is classical and differs in no way from that 
seen in the absence of cranial injury. 

Symptoms and Signs. — The symptoms, like the pathology, are classi- 
cal also. They include high fever, delirium or stupor, stiff neck, headache, 
incontinence and so forth. In the non-operable group of these injuries a 
fracture of the temporal bone, the cribriform plate or into the cavity of 
one of the paranasal air sinuses usually can be demonstrated as the source of 
the infection. In the operable group the source practically invariably is 
found in the wound. There are the usual signs to be elicited by neu- 
rological examination. The cerebrospinal fluid will be under a high pres- 
sure, there will be pleiocytosis and the total protein content will be elevated. 
If bacteria are present, a drop in the cerebrospinal fluid sugar and chloride 
content will be a constant finding. On the other hand a rise will be a 
favorable prognostic sign and usually will coincide with clinical improve- 
ment. Cultures may or may not be positive. 

Diagnosis. — The diagnosis is made from the cerebrospinal fluid find- 
ings. The infecting organism may be identified by cultures taken from 
the cerebrospinal fluid, the blood stream, the nasal cavity or the operative 
wound. 

Treatment. — This is notoriously, but not invariably, unsuccessful. The 
use of sulphanilamide in initial and maintenance doses sufficient to main- 
tain a concentration of lo mgm. per cent, of drug in the blood stream is 
very effective for hemolytic streptococcal and pneumococcal infections. 
Alkalis should be administered by mouth to prevent acidosis, and care 
should be taken to forestall the development of anemia by giving blood 
transfusions when indicated. The administration of the drug should be 
discontinued when the white blood cell count begins to drop to avoid the 
danger of agranulocytosis or if other severe toxic manifestations appear. 
Appropriate anti-pneumococcic serum should be used in combination with 
sulphanilamide in the treatment of pneumococcic meningitis. There is 
also some reason to believe that in larger doses it may be effective against 
influenzal bacillus meningitis. For the latter there is available a specific 
anti-serum. In all these infections, and in the staphylococcic as well, 
older therapeutic methods should not be neglected, however. Not a few 
such cases of meningitis were cured before the advent of sulphanilamide 
by a combination of extreme hydration and lumbar drainage every 4 
hours. To do this, fluids must be forced to the point of 6,000 c.c. every 
24 hours and the lumbar sac drained dry of cerebrospinal fluid every 4 
hours day and night. Tidal drainage to care for incontinence, transfusions 
for anemia and high caloric high vitamin diets all are essential adjuncts. 
Such therapy must be continued until the sugar, chloride, protein and 

Vol. VI. 339 



BRAIN ABSCESS 136 (21) 

cellular content of the cerebrospinal fluid have become fixed at normal, 
regardless of earlier symptomatic improvement. The administration of 
serum intra-thecally should be avoided as its presence there is apt to 
cause the development of a subarachnoid block and thus prevent drainage 
of the cerebral spaces by a lumbar tap. 

Ratio of Occurrence. — In the non-operable types of hospitalized cranio- 
cerebral injuries, meningitis occurs in about 3^ of i per cent, of the cases. 

Mortality. — Before the advent of sulphanilamide the mortality was 
above 80 and below 100 per cent. It has doubtless improved since, but 
the figures are not yet available. 

Brain Abscess 

This is a strictly surgical and an extremely complicated problem and 
can only be touched on briefly here. It is discussed also in Vol. VI, 
Chapt. IV. 

Pathology. — Brain abscesses are of two types. The commonest is the 
encapsulated. This type of abscess may be either single or multiple, 
usually only single in cranio-cerebral injuries, cerebral or cerebellar and 
subcortical, cortical and sub- or extra-dural. The abscess consists of a 
collection of infected necrotic material contained within a relatively thick- 
walled capsule. It may increase in size and rupture into the ventricular 
or meningeal spaces and cause meningitis. It may become sterile and be 
absorbed or calcified or remain as a sterile cyst. The second type is the 
encephalitic. This in cranio-cerebral injuries usually is the result of a 
direct spread of infection from the cranium or scalp. It has no capsule, 
spreads by radial infected thrombi and shortly produces meningitis or 
ventriculitis. It is most commonly seen otherwise as a metastasis from 
some distant source of infection. 

Symptoms and Signs. — The symptoms and signs of both types are 
those of an expanding intracranial lesion with or without evidence of an 
infection in the cranium or scalp. Although there is usually a moderate 
cerebrospinal pleiocytosis, this is by no means invariable. The chemistry 
usually is normal except for a possible moderate increase in total protein. 
The intracranial pressure usually is high but may not be greatly elevated. 

Diagnosis. — The diagnosis may be extremely difficult, frequently has to 
be made with the aid of ventriculography or encephalography and is usually 
confirmed only by exploratory needling of the suspected areas of the brain. 

Treatment. — Treatment is exclusively surgical and predicates drain- 
age of the abscess preferably either by the insertion under the eye of the 
Mosher copper wire cone drain or induced extravasation after the method 

Vol. VI. 339 



136 (22) CRANIOCEREBRAL INJURIES 

of J. E. J. King, Its rate of occurrence among cranio-cerebral injuries 
and its mortality are not known. The liability of these cases to late 
symptoms, however, must be high on account of the associated cortical scars. 



Osteomyelitis and Infected Scalp Wounds 

These are characteristic of a relatively benign infection of the cranial 
bones or of the scalp. There is a tendency to abscess formation locally. 
The infection almost never spreads through the diploe. A similar type of 
osteomyelitis sometimes occurs in children in connection with furunculosis 
of the scalp and in the absence of trauma. 

Symptoms and Signs. — They are those of a persistently draining 
wound with bare dead bone frequently palpable in its depths. 

Diagnosis. — This is made from the classical signs of local inflamma- 
tion and either with or without the help of the x-ray. 

Treatment. — This includes excision of the dead bone and drainage of 
the infection and is always surgical. 

Ratio of Occurrence and Mortality. — These figures are not available. 

Simple and Complicating Fractures of the Vault and Base of 
the Skull, other tlian Compound or Depressed Fractures 

Simple Linear or Comminuted Fractures 

Simple linear or comminuted fractures probably are the commonest 
associate of cranio-cerebral injuries. They are still made to serve as the 
focal point of medicolegal interest in these cases, and the medical pro- 
fession still persists in the useless differentiation between those of the base 
and those of the vault. They are distinguishable from complicating linear 
and comminuted fractures by the fact that they do not involve the ac- 
cessory paranasal sinuses and the cavities of the nose, ear and mastoid. 
Their presence has no significance other than to serve as evidence that 
the bone containing the fracture came in contact with some stationary or 
moving object. Their importance lies in the damage they cause to vessels 
and nerves which have been in direct contact with, them at the time of 
their formation. 

Diagnosis. — The diagnosis of a linear or comminuted fracture is made 
by x-ray. It should not be forgotten, however, that the x-ray films are 
not necessarily lOO per cent, correct, and that tlie coincidence of adjacent 
shadows, the angle of the ray and the like may on the one hand prevent 
visualization of fracture lines that are actually present, while on the other 

Vol. VI. 339 



OTHER INJURIES WITH SIMPLE FRACTURES 136 (23) 

hand the appearance of normal venous markings may lead to a diagnosis 
of fracture when there actually is none. 

Treatment. — Simple linear and comminuted fractures of the skull of 
themselves call for no treatment. 

Ratio of Occurrence. — This is not known. 

Mortality. — There is none. 

Injuries Other Than Those of the Cerebrum, Cerebellum and Meninges 
that are Associated with simple Fractures 

If properly placed, simple linear or comminuted fractures may damage 
certain of the cranial nerves and blood vessels. The nerves are commonly 
the optic, any of the oculomotor nerves, the trigeminal and the facial. 

Diagnosis. — The diagnosis is obvious in every case as soon as the 
physician demonstrates the motor or sensory palsy that necessarily is 
associated with the nerve injury. Particular care should be taken, how- 
ever, to recognize blindness, loss of corneal sensibility and paralysis of the 
orbicularis palbebrarum and frontalis muscles. Whenever there is a par- 
tial or complete division of the optic nerve, the patient or his legal repre- 
sentative should be notified at once. Only in this way can the doctor 
surely protect himself against later claims that the loss of vision is due 
to his treatment or lack of it. This is particularly important, if the patient 
is comatose or uncooperative and, as a result, fails to recognize his dis- 
ability until after a relatively long period of time. If the division of the 
nerve has been complete, and provided there has been no interruption of 
the retinal blood supply, there will be a loss of the light reflex and after 
a suitable interval the ophthalmoscopic signs of secondary optic atrophy. 
Loss of corneal sensibility from fifth nerve injury and inability to close 
the eye from facial nerve injury, if not recognized early, may lead to 
corneal scars and interference later with vision because of them. 

Treatment. — There is no effective treatment for a division of the optic 
nerve or the resultant blindness. Corneal scars can be prevented in most 
cases by the application of an air-tight goggle or similar covering to the 
affected eye. This produces a moist chamber and prevents direct or in- 
direct damage to the corneal epithelium. In severe cases the lids can be 
sutured. Suitable goggles can be obtained from many stores or may be 
made of individually shaped celluloid on a spectacle frame. In the facial 
nerve cases electrical stimulation of the paralyzed muscles, daily massage 
of the face from the corner of the mouth upward toward the external 
auditory meatus and finally implantation of subcutaneous fascial or 
muscle slings should all be used as part of the local therapy. 

Vol. VI. 339 



136 (24) CRANIO-CEREBRAL INJURIES 

If the optic nerve is severed, the bUndness is complete and permanent. 
The oculomotor, the fifth and facial nerves may all be interrupted only 
physiologically, although the symptoms be those of an anatomical divi- 
sion. In such cases, provided adequate temporary care of the muscles 
and of the eye ball is taken until conduction is again resumed, later dis- 
ability will be nil. Furthermore, since such injuries to these nerves occur 
to their post -ganglionic portion, even complete anatomical division need 
not predicate permanent loss of function, providing their peripheral supply 
is kept in order until regrowth of the axones can take place. This process 
may, in certain cases, be expedited by suture, decompression or anasta- 
mosis. The end results, therefore, will depend in part on the care of their 
peripheral supply and in part on the success of the artificial reparative 
processes that are resorted to to promote regrowth or replacement of the 
destroyed axones. 

Ratio of Occurrence. — This is not known. 

Mortality. — There is no mortality. 

Traumatic Arterio- Venous Aneurysm 

For practical purposes the only blood vessel within the cranium that 
is injured in association with uncomplicated linear or comminuted frac- 
tures of the skull is the internal carotid artery. Others such as the venous 
sinuses and the middle meningeal arteries, when injured, produce syn- 
dromes that are of sufficient importance to justify segregation as extra- 
or sub-dural hematomas. A fracture in the middle fossa involving the 
body of the sphenoid bone may either rupture the wall of the carotid 
artery at the time or damage it sufficiently so that it will break a few 
days later. Because of the anatomical relationships the part of the artery 
that is injured is that which lies within and surrounded by the cavernous 
sinus. Thus arterial blood is introduced into a large vein, and since the 
collection of this venous blood normally is from the contents of the orbit, 
such an arterio-venous aneurysm produces a pulsating exophthalmos. 

Symptoms and Signs. — The symptoms are associated chiefly with a 
constant roaring in the patient's head, the development of which may 
follow within a few hours of, or some days after, a blow on the skull. A 
bruit can be heard through a stethoscope applied over the affected eye 
and often over a large adjacent area of skull. There will be a slowly de- 
veloping pulsating exophthalmos with all the eye signs associated with 
either a mild or severe degree of protrusion of the eyeball. There may be 
varying degrees of extra-ocular muscular palsy. X-ray examination usu- 
ally is negative, and there need not be any severe associated brain injury. 

\'oL. VI. 339 



COMPLICATING FRACTURES 136 (25) 

The bruit and symptoms will be improved or done away with, if the com- 
mon or internal carotid artery is closed by pressure on the neck. 

Diagnosis. — The diagnosis is made on the history of the subjective 
intracranial roaring, the exophthalmos and the temporary relief of symp- 
toms following closure of the involved carotid artery. 

Treatment. — The treatment may be only palliative at best. It is 
more likely to be effective, if instituted very early, and if the break in the 
arterial wall is minimal. Therapy is both possible and relatively ineffec- 
tive because of the anastamoses through the circle of Willis. It is accom- 
plished by the permanent closure of the internal or common carotid artery 
in the neck. Before this can be done without undue risk of hemiplegia 
or death the collateral circulation must be stimulated and increased lo- 
cally. This can be done best by the patient himself and should be started 
at the earliest possible moment. He compresses his common carotid 
artery against the cervical spine in such a way as to close it completely. 
The artery should be held closed until the patient begins to feel faint. 
The length of time of closure thus will increase automatically, and when 
it reaches 30 minutes without the production of any subjective symptoms, 
permanent operative closure can be undertaken. The preliminary pro- 
cedure usually requires about seven weeks. The operation is done best 
in two stages. In the first the common carotid artery is exposed in the 
neck and closed by the application of a Matas aluminum band. Two 
weeks or more later the internal carotid artery is exposed through the 
same or a higher incision and also closed by the same method. These 
wounds must be completely aseptic and should be drained for at least 24 
hours but no longer. Hemostasis must be most meticulous. A spreading 
thrombosis, which gradually fills the carotid tree on the operated side, is a 
possible, but unpredictable, result of such an artificial occlusion. Death 
necessarily ensues, if this happens. 

Complicating Fractures of the Skull 

Complicating fractures of the skull are those linear or comminuted 
fractures that are neither depressed nor compounded and that involve in 
their course the paranasal air sinuses, the cribriform plate and the cavities 
of the nose, ear and mastoid. 

Fractures of Temporal Bone 

The most common are the fractures of the temporal bone, which extend 
into some part of the ear either with or without involvement of the mastoid. 
Vol. VI. 339 



136 (26) CRANIOCEREBRAL INJURIES 

Pathology. — Their presence permits communication between the sterile 
meningeal spaces and the possibly infected ear or mastoid cavities. Some 
degree of brain injury always is associated with them. 

Symptoms and Signs. — The symptoms include dizziness, unsteadiness, 
nystagmus, loss of hearing, facial palsy and loss of the sense of taste. Any 
one may be either transitory or permanent. This communication between 
the meninges and the ear is certain, if cerebrospinal fluid escapes from the 
ear, and is probable, if there is any amount of bleeding from the same 
source. There may be associated damage to the seventh and eighth cra- 
nial nerves, the drum or the labyrinth. Meningitis by direct extension is 
a possibility at any time up to 2 weeks after the injury. 

Diagnosis. — The diagnosis is made most surely by the demonstration 
of cerebrospinal fluid flowing from the external auditory meatus. Other 
signs are those provided by means of x-ray films, by a hematoma over the 
mastoid or a fracture line visible through the otoscope in the middle or 
inner ear. Acute traumatic labyrinthitis from labyrinthine hemorrhage 
and associated with deafness may, by the Barany or caloric irrigation tests, 
show either hypo- or hyper-activity of the damaged labyrinth. 

Treatment. — The treatment is to avoid all manipulation of the ear 
and especially to avoid plugging or irrigating the canal. If there is an 
escape of cerebrospinal fluid, it is necessary to keep the intracranial pres- 
sure low by early and frequent lumbar punctures. This permits collapse 
of the subarachnoid space adjacent to the meningeal tear and favors heal- 
ing of the arachnoid membrane. 

When disabling labyrinthine symptoms have been present and un- 
abated for a year or more, it is probable that they will be permanent. 
Any relief from the unsteadiness and vertigo will come only from the 
patient's ability to adjust himself to the new conditions under which he 
is forced to live, unless he can get help from some surgical procedure. 
If his intellectual level is high and his morale good, this latter may not 
be necessary, but if adjustments cannot be made, its adoption may well 
prove indispensable. The degree of neurosis, of lowering of the morale 
and of the tendency to live a more and more secluded and antisocial life 
will be the factors that determine the future treatment. These cases fall 
within the group that is covered by the diagnosis Traumatic Aural Vertigo 
or Traumatic Meniere's Syndrome. Successful treatment of this chronic 
disabling lesion depends upon the recent demonstration that one's sense 
of position in space is normal only when either the integration and joint 
action of both labyrinths is perfect, or when the control is vested in one 
labyrinth alone, the other being completely dead. From this premise and, 
more recently, because of the increasing success of the operative treatment 

Vol. VI. 339 



COMPLICATING FRACTURES 136 (27) 

of non-traumatic Meniere's syndrome, methods looking toward completing 
the destruction of the already partially destroyed and damaged labyrinth 
have been advised and used. The most successful is that surgical pro- 
cedure in which the vestibular part of the eighth nerve on the affected 
side is divided in the posterior fossa of the skull. In this way a certain 
functional destruction of the damaged labyrinth is assured, and there is 
no interference with the hearing of the ear in question. Complete relief of 
symptoms may be expected in these traumatic Meniere's cases in about 
85 per cent, of the patients as contrasted with the 100 per cent, relief 
attained by the same therapy in the non-traumatic group. 

Ratio of Occurrence and Mortality. It has proved impossible to collect 
these figures with any degree of accuracy. 

Fractures Involving Cribriform Plate or Paranasal Sinuses 

Fractures involving the cribriform plate or paranasal sinuses, while 
less common, are much more serious. 

Pathology. — In either case, communication with the nose is established 
and the local pathological picture is characteristic of, and depends upon, 
the upward spread of infection from the nasal cavities. 

Diagnosis. — The diagnosis is made by x-ray, by the escape of the 
cerebrospinal fluid from the nose with or without blood or by the demon- 
stration of air inside the skull. By far the most dangerous cases are those 
with the cerebrospinal fluid rhinorrhea. 

Treatment. — The chances of treating this condition successfully by 
repeated lumbar punctures are extremely remote. Yet, if it is not stopped 
promptly, meningitis is an inevitable certainty. An early operative ex- 
posure of the fracture and upper end of the fistulous tract followed by 
plastic closure of the dural tear is essential. This should be undertaken 
as soon as the patient's condition warrants and with a full appreciation 
of its magnitude. 

Fracture of Posterior Wall of Frontal Sinus 

Fracture of the posterior wall of the frontal sinus is a not infrequent 
form of fracture of the skull with the compounding into the nasal cavi- 
ties rather than through the scalp. The diagnosis is made by x-ray. 

Treatment. — There is no one rule for treating these cases. Each is an 
individual problem, and treatment, in the last analysis, depends upon 
whether or not the surgeon believes that the mucous membrane lining of 
the sinus is torn. If he does, the sinus should be entered surgically, the 

Vol. VI. 339 



136 (28) CRANIOCEREBRAL INJURIES 

membrane removed, the posterior wall excised and the sinus cavity and 
epidural space drained. If he does not, there need be no operative inter- 
ference. There is no certain way of determining the presence of such a 
tear except by demonstrating air either in or outside of the meninges. 
Even then, if the patient is improving steadily, operative interference w^ill 
be neither necessary nor wise. If symptoms persist or increase, or signs 
of meningeal irritation arise, operation is imperative. It is probable that 
the great majority of these fractures are asymptomatic. The occurrence 
of meningitis has been given in one series as 0.8 per cent. 

Mortality and Ratio of Occurrence. — These figures are not available. 

Aerocele 

The abnormal presence of air in the skull is extremely rare and usually 
associated with a fracture of one frontal sinus. The air may not appear 
for some days and then only after a sneeze or an attempt by the patient 
to blow his nose. Its presence indicates a communication between the 
nose and the meninges and, as such, in all probability calls for operative 
interference. 

Complications Due to Necessary Treatment 

Because of their severity and situation many cranio-cerebral injuries 
require emergency treatment. This must be provided regardless of 
whether or not it creates a situation that later and in its turn requires 
further therapy. At this later date the original injury has long since 
healed, and although originally arising as a complication of the former, 
the later condition will be an entity in itself and have its own signs, 
symptoms and pathology and require its ow'n specialized therapy. Neces- 
sary treatment for this type of complication invariably is surgical. 

Bilateral Subtemporal Decompression 

As the result of necessary operative procedures, patients who have 
sustained cranio-cerebral injuries are left, at times, with bilateral temporal 
bony defects. If both are of any significant size, late closure of at least 
one may prove to be essential to the patient's final and complete recovery. 

Pathology. — There is an absence of a part of the squamous temporal 
and often adjoining portions of the frontal and parietal bones on both 
sides of the skull. The bone defects overlie defects in the dura which are 
of approximately the same size. The vertical or inverted horseshoe 

Vol. VI. 339 



POST-OPERATIVE DEFECTS IN SKULL 136 (29) 

shaped scar in the scalp and temporal muscle usually is adherent to the 
underlying cortex or arachnoid or both. These and the soft tissues of the 
scalp all are fused into one fibrous mass at the periphery of the defect and 
in turn are firmly adherent to its edge of bone. 

Symptoms and Signs. — The chief symptom is a feeling of "looseness 
of the brain inside the skull" so that the "brain rattles". This creates a 
marked sense of insecurity. The pulsation of the scalp in the region of 
the defects is another equally constant but less disturbing symptom. 
There are no significant signs in the defects themselves other than the 
scalp scar, the constant pulsation and the filling and emptying of the 
defect with every change of position of the patient's head. 

Treatment. — The treatment is operative. The essential steps are to 
create new edges of bone and dura, separate all adhesions to the cortex 
and fill the dural defect with a free transplant of fascia lata. The bony 
defect in this area need not be filled. Usually it is only necessary to close 
one side in order to relieve the symptoms. Both sides can, however, be 
repaired should it prove necessary. 

Post-operative Defects in the Skull Bones 

For the most part, artificially produced cranial defects following 
treatment of cranio-cerebral injuries are small. Their repair usually is 
only necessary for esthetic reasons and is, therefore, most liable to be 
required for those defects that lie outside of the hair-line. Among those 
that are within the hair-line, repair is required only for the larger ones 
and only then if they overlie the motor cortex. The large majority have 
been at the least the site of drainage and usually have been infected as 
well. For that reason their repair always must be postponed until such 
time as the surgeon can be reasonably sure that his operation will not 
stir up a residual quiescent infection that otherwise would not become 
activated. Such a mishap will lead to the extrusion and loss of the 
transplant and may even be directly followed by meningitis or other major 
intracranial infection. It should be assumed, until disproven, that all 
bone defects are associated with underlying defects in the dura as well 
as being the site of widespread adhesions between that membrane, the 
bone edge, the cortex and the scalp. Essential parts of every reparative 
operation are those which free all these adhesions and close the dural 
defect by a transplant of fascia lata. If the bony deficiency is filled 
without these added steps, the strong probability is that there will be no 
subsequent relief of the patient's symptoms. 

Bony defects that require filling are either supra-orbital or parieto- 

VoL. VI. 339 



136 (30) CRANIOCEREBRAL INJURIES 

frontal. Deficiences in the temporal and occipital bones being in the former 
instance beneath the temporal muscles and in the latter under the heavy 
neck muscles do not require repair provided the dura is intact. 

Supra-orbital Defects. — These are of two types and are classified in 
accordance with whether the supra-orbital ridge is absent or not. In 
neither case is there any involvement of the frontal sinus. If the ridge is 
gone, there is little that can be done to correct the defect and replace the 
ridge. Like the frontal sinus fistulas this is a problem which should be 
referred to, and will tax the ingenuity of, the "plastic surgeon". The 
best cure is prevention. The supra-orbital ridge usually is absent because 
it has been removed as part of the treatment of a compound fracture in 
this region. This removal should never be permitted under any circum- 
stances, if it is at all possible to avoid it. 

Those defects that form part of a fistulous tract which leads into an 
air sinus, usually frontal, must be cared for by a surgeon skilled in the 
more complicated methods of plastic repair and do not properly come 
within the scope of this discussion. 

Parieto- Frontal Defects. — The filling of deficiences of the parietal and 
frontal bones exclusive of the supra-orbital regions commonly is advised 
for one of three reasons. The first is cosmetic and applies only to those 
defects that are outside of the patient's hair-line. The second is because 
the patient is fearful that the presence of the defect will render him more 
liable to injury than he would be if the skull was intact. This fear is 
justified only in the larger defects, but it should not be overlooked that, 
even if not justified by the size and location of the deficiency, the fear 
itself may get so out of hand as to afTect the patient's morale and even- 
tually to produce a neurosis. In such cases justification for the reparative 
procedures may be found in the emotional effect rather than the anatomi- 
cal size of the defect. The third reason commonly is thought to lie in the 
patient's greater liability to convulsive seizures or peripheral palsies while 
the artificial opening remains unclosed. It cannot be emphasized too 
strongly that the absence of bone in these conditions has absolutely noth- 
ing to do with either the initiation or continuance of convulsive seizures 
or peripheral palsies. These distressing complications arise out of cortical 
and subcortical pathology that varies all the way from scar tissue and 
widespread cellular destruction to adhesions between the cortex and scalp. 
Replacement of absent bone will do nothing for such symptoms unless, 
and until, it is accompanied by appropriate excision of cortical scars, re- 
lease of adhesions and repair of dural defects. 

Pathology. — The pathology of bony defects is that associated with the 
absence of both tables of bone locally and associated adhesions between 

Vol. VI. 339 



FOREIGN BODIES 136 (31) 

the scalp, the meninges, the bone edges and the cortex. Previous infec- 
tion increases this tendency to mat together. 

Symptoms. — Unless the dural opening is large, these symptoms usu- 
ally are limited to a feeling of insecurity and to the irritation and fear 
caused by the consciousness of a visible deformity. 

Signs. — The objective sign is a visible or palpable depression under 
the scalp at the site of the absent bone. Pulsation may or may not be 
visible, usually not in the older ones, but, except in the small trephine 
hole defects, usually is palpable. 

Treatment. — The preferable method of closure depends upon the size 
of the bony opening that is to be filled. The material used should, if 
possible, always be in the nature of an osteo-periosteal transplant. This 
transplant is obtained most easily, even for large defects, from adjacent 
areas of skull. To obtain it, an appropriately sized piece of outer table 
to which periosteum is still attached is removed in one piece and moved 
into the defect. This procedure is known as the Konig-Miieller operation. 
For small defects a button of bone from an area within the hair-line may 
be removed with the old-fashioned hand button-trephine and used to fill 
the deficiency that is visible. Bone chips and bone fragments may be used 
also in small defects. In all cases, however, the asepsis must be absolute, 
hemostasis most meticulous and manipulations gentle since sepsis, whether 
from a previously contaminated wound, a hematoma, or tissue necrosis 
from improperly handled tissue or too-tight sutures, will cause the wound 
to break down and the transplant to be extruded as a foreign body. 
Practically every reasonable material has been recommended and used for 
the repair of bone defects in the skull. Included have been silver plates, 
perforated and non-perforated celluloid, pieces of ribs and costal cartilages, 
homogenous and heterogenous bone, bone obtained at post-mortem and 
subsequently sterilized and bone flaps and fragments of comminuted frac- 
tures whether compounded or not. No method or material has been as 
generally satisfactory as the Konig-Miieller and the transplant from the 
adjacent outer table, however. 

Foreign Bodies in Cranio- Cerebral Wounds 

This complication manifests itself in such wounds in much the same 
way that it does in any surgical wound. In the absence of infection a 
foreign body may remain in place for years and cause no symptoms 
whatsoever. If infected, however, the wound will not heal permanently 
until the foreign body is removed. In cranio-cerebral wounds the usual 
foreign bodies are silk stitches or knots, silver clips, forgotten pieces of 

Vol. VI. 339 



136 (32) CRANIO-CEREBRAL INJURIES 

cotton, broken pieces of drainage material, unabsorbed muscle postage 
stamp grafts and dead bone. 

Broken Lumbar Puncture Needles 

The breaking of a lumbar puncture or long injection needle is, or 
should be, recognized at the time it occurs and at least at the finish of 
the puncture by the discovery of the break when the needle is withdrawn. 
It is an occasional unavoidable accident inherent in the treatment of 
uncooperative and at times maniacal patients. The patient will complain 
of no symptoms and may not know of the incident. The fragment 
usually is in the lumbar but may be in the high cervical region. 

Pathology. — The fragment is never wholly in the spinal canal at first. 
For a variable period of time after the break, some part of it will be found 
sticking through the ligamentous structures or into the bony wall. 

Symptoms and Signs. — Beyond identifying the site of the puncture in 
the skin, physical examination will yield little information. X-ray exam- 
ination, on the other hand, is essential. This should be made at once. 
Stereoscopic films in both the lateral and anteroposterior planes should be 
taken. Following the x-ray examination the patient should be moved as 
little as possible, to avoid shifting the position of the fragment. 

Treatment. — This should consist of the operative removal of the frag- 
ment as soon as possible. The operation should be formal, and no time 
should be wasted in trying to find the fragment through a small incision 
with an inadequate kit and no assistance. It should be carried out 
through a trap-door incision which is hinged on one side of the mid-line 
and shaped like a half circle in the centre of which is the approximate lo- 
cation of the needle end. In this way, a segment of a circle will be turned 
across the mid-line which, if cut to a proper depth, will expose the lumbar 
fascia. The end of the needle usually is visible at this point, but if not, a 
similar trap-door of fascia, turned in the other direction, can be cut. 
Further steps follow those of the classical laminectomy. 

Post-operative Cerebrospinal Fluid Fistulas 

The drainage of cerebro-spinal fluid through a fistulous opening in an 
operative wound, that is uninfected and that does not include a foreign 
body, usually can be controlled by the frequent application of large 
amounts of thymol iodide. If this is not effective, the wound should 
be incised, the fistulous tract removed and the wound carefully resutured 
layer by layer with interrupted silk stitches. Enough lumbar punctures 

Vol. VI. 339 



IN THE NEW-BORN 136 (33) 

should be done to keep the intra-cranial pressure constantly at or below 
the normal level. 

Fungus Cerebri 

This is an apparent protrusion of the cortex through coinciding open- 
ings in the dura, bone and scalp and occurs only in cranio-cerebral injuries 
when there is a severe infection in the wound. Meningitis, encephalitis, 
septicemia and osteomyelitis usually are present as well. Its presence is 
due to a combination of increased intracranial pressure plus a rapid growth 
of excessive amounts of granulation tissue on the surface of the infected 
brain. From the therapeutic point of view it is important only because 
it must not be cut off. To do so leads only to its regrowth to an even 
larger size or, what is more likely, to a spread of the encephalitis and 
death of the patient. It will disappear without further treatment when 
the infection has been controlled and the intracranial pressure re-estab- 
lished permanently at normal. 

Incontinence and Lumbar Puncture 

It is at times necessary to do many lumbar punctures in a patient 
who remains incontinent of urine for a relatively long time. If uncor- 
rected, such constant lying in a wet bed will produce a high incidence of 
infection in the skin puncture wounds and may lead to meningitis. Even 
at the best it forces the operator to reduce the number of his punctures 
to a minimum that is unsatisfactory and inefficient from the point of 
view of the cranio-cerebral lesion. This can be avoided by the use of 
the tidal drainage apparatus for the bladder. Such an apparatus will 
keep the patient dry, obviate residual urine, reduce the severity of the 
infection that is associated with other types of constant drainage of the 
genito-urinary tract, prevent shrinkage or distention of the urinary 
bladder and simplify what is otherwise a very difficult nursing problem. 
If the apparatus is adjusted properly, either male or female patients can 
wear an inlying urethral catheter indefinitely, provided only that it be 
removed, cleaned and sterilized once a week. The apparatus must be 
sterilized also at the same time and care taken to see that the irrigation 
fluid is kept free of contamination by bacteria at all times. 

Cranio-Cerebral Injury in the New-born 

Although not commonly recognized as being part of the problem of 
cranio-cerebral injuries, it is nevertheless true that intracranial hemorrhage 
Vol. VI. 339 



136 (34) CRANIOCEREBRAL INJURIES 

of the new-born and the general problem of fetal cranio-cerebral injuries, 
produced before and during labor, should be included therein. To be sure 
the pathology is conditioned somewhat by the method of production and 
the antecedent circumstances but, from the larger point of view, it is 
now possible, just as in the adults, to identify a common fundamental 
non-operable group of lesions to which may be added certain operable 
conditions, bony and meningeal injuries and complications arising out of 
general bodily states and local infection. 

While fetal cranio-cerebral injury unquestionably is associated always 
with the general problem of labor, the primary causative factor is found 
not in the application of external violence to the head but rather in a 
pathological extension of a normal physiological process. It has now been 
established beyond reasonable doubt that the full-term human fetus nor- 
mally exists in the uterus in a state of cyanosis. With this goes a blood- 
oxygen unsaturation that is nearly twice that sufficient to make the 
cyanosis visible. At birth this oxygen unsaturation is increased by one quar- 
ter because of the impairment of the placental circulation by the con- 
tracting uterus. Thus, at this time, the arterial blood of the fetus contains 
less oxygen than the venous blood of the mother. Any increase in this 
oxygen unsaturation will be pathological. It will be associated with tissue 
anoxia and marked generalized venous congestion and is, by definition, 
asphyxia. It will vary in degree and may produce a wide variety of tissue 
changes including edema, petechial and coalescing hemorrhages, throm- 
bosis, cellular destruction, an accumulation of lactic acid in the blood 
stream, alterations in the respiratory and pulse rates, a fall in blood pres- 
sure to shock levels and finally death. The asphyxia alifects the entire 
fetus and all its organs including the brain. It is produced by an inter- 
ference with the placental circulation and may, therefore, be present long 
before labor has begun. Since it is probable that the normal fetus in 
utero makes respiratory movements, which are continued as normal 
breathing coincident with the termination of the placental circulation, 
inhalation of vernix, meconium and liquor may take place before or during 
labor. Their mechanical obstructive effect may render the already exist- 
ent asphyxia more asphyxial. It should be emphasized that pathological 
asphyxia cannot be measured in terms of either cyanosis or absolute anox- 
emia, and its presence can be recognized only by a demonstration of ab- 
normalities in the placental circulation or of signs known to be associated 
with tissue anoxia of high degree. The organs most commonly the seat 
of resultant demonstrable changes are the liver, lungs, heart, kidneys, in- 
testinal tract, spleen, adrenals, thymus, spinal cord and brain. The seat 
or seats of such maximum involvement will determine the symptomatol- 

VoL. VI. 339 



IN THE NEW-BORN 136 (35) 

ogy, while trauma locally only increases the extent and severity of this 
damage to any underlying structure. 

Fundamental Intracranial Pathology in Cranio- Cerebral 
Injuries of the New-Born 

Insofar as it affects the brain, the basic asphyxia of the new-born and 
its after-effects are completely analogous to the vasovagal reflex and the 
changes it institutes in the adults. Associated with, and resulting from, 
the asphyxia may be an increased cerebral venous pressure, congestion 
and dilation of the venules, perivascular and perineuronal edema, con- 
gestion and dilatation of the cerebral veins, an increase in intracranial 
and cerebrospinal fluid pressure, cortical and subcortical thromboses and 
petechial and coalescing hemorrhages and finally, rupture of the external 
and larger veins. Such changes, if appropriately placed and of sufficient 
extent, as the result of the asphyxia alone may terminate in all degrees 
of cortical and subcortical cellular destruction. In later life these end 
results may be apparent as disturbances varying from porencephaly and 
hydrocephalus ex vacuo through epilepsy and idiocy to any degree of 
spastic paraplegia or Little's disease. In the earlier fatal cases autopsy, 
if death has been due to the intracranial condition, may demonstrate in- 
traventricular, subarachnoid and subpial hemorrhages complicating cere- 
bral, cerebellar and medullary edema and limited only by the size and 
location of the ruptured vein. If the intracranial condition is merely a 
minor complication of other fatal organic injuries, then there may be no 
more than cerebral congestion and edema. Thus the diagnostic possi- 
bilities as applied to the cranial contents of the newborn vary from 
congestion and edema through intracortical, subarachnoid and subpial 
hemorrhages to intraventricular hemorrhage from rupture of the vessels of 
the choroid plexus, but the etiology is the same in every case and is found 
in the fetal asphyxia. All these conditions are analogous to the non-operable 
cerebral lesions in the adult. To them are added the changes that result 
directly from trauma. They are classed as a group under the name of 
asphyxial type of intracranial injury in the new born. 

Additional Cranial and Intracranial Pathology in Crania- 
Cerebral Injuries of the New Born 

The more extensive and additional pathology, that is commonly as- 
sociated with varying degrees of trauma to the fetal head, never occurs 
alone but always as an accompaniment of the results of the associated 

Vol. VI. 339 



136 (36) CRANIO-CEREBRAL INJURIES 

fetal asphyxia. However, it may prove to be impossible, in a given case, 
to separate causes and results from one another or even to be sure whether 
trauma actually has been a factor or not. Consequently, it is only in the 
clear cut cases that this latter diagnosis can be added to that of asphyxial 
intracranial damage as an explanation of the symptoms or post-mortem 
findings. Attempts to diagnose completely every case should be persisted 
in, however, because a demonstration of a traumatic factor in the causa- 
tion of the symptoms may prove to be the one thing needed to justify 
the predication of an operable lesion. This, if treated at once and prop- 
erly, may be prevented from causing death or, what is worse, prolonged 
invalidism followed by death. 

The sources of such trauma are various. Some arise commonly, but 
not necessarily, out of methods adopted by the obstetrician to terminate 
labor. The less obvious but more usual sources are found in the pro- 
cesses of labor itself, however. The former predicate an unsatisfactory 
or difficult labor as the reason for termination and, therefore, of necessity 
also predicate a high degree of fetal asphyxia. Compression of the head 
by the application of such external force will, at the very least, increase 
the venous congestion and rupture veins that otherwise would not break, 
or lead to a more serious edema with its associated wider spread of an- 
oxia and cellular damage. It is characteristic of both kinds of trauma, 
however, to be of a type the application of which is relatively slow and 
prolonged. This is in contradistinction to the methods by which adult 
injuries are caused. Whether produced by some such procedure as the 
misapplication of high forceps or whether due to some type of uterine 
dystocia, the ultimate effect is the same and results in a slow intermittent 
squeezing of the skull. This leads to an excessive overriding of the indi- 
vidual bones. Some degree of this moulding is a normal accompaniment of 
all labor. When carried beyond this point, however, its harmlessness de- 
pends upon the margin of extensibility of the bridging veins which cross 
from the cortex to the venous sinuses, the elasticity of the dural septa and 
the degree of compression of the cranial ends of the jugular veins. Thus, 
early rupture of the membranes with a dry labor, cephalopelvic dispro- 
portion with arrest of the descent of the head or prolongation of the sec- 
cond stage of labor from a stiff undilatable cervix and the like, all lead 
to excessive increase in venous congestion locally. The bridging veins 
become overdistended, and their potential powers of elongation thus are 
done away with. This factor together with no more than normal over- 
lapping at the suture lines may cause them to rupture. When, in ad- 
dition, excessive overlapping is required because of delivery from an 
unfavorable position, a small jjelvis, the application of forceps with traction 

Vol. VI. 339 



IN THE NEW-BORN 136 (37) 

or injudicious traction on the head in a breech delivery, it is obvious that 
not only will the bridging veins rupture, but that such strain is put upon 
the falx and tentorium as to cause them to tear and in turn lead to rup- 
ture of the vein of Galen and the laceration of the walls of any of the 
venous sinuses. Further traumatic excesses, such as a delivery by the 
Scanzoni maneuver, the forceable traction of the fetal head past a pro- 
tuberant promontory or through a rachitic flat pelvis or strong traction 
on badly misapplied forceps only add more trouble in the form of fractures 
through the foramen magnum with or without a broken neck, depressed 
and egg-shell fractures and expanding lesions such as result from a rupture 
of the middle meningeal artery. Any of these major injuries may be ac- 
companied by surgical shock. This has been unrecognized as such in the 
past because it has masqueraded under the fanciful title of asphyxia pal- 
lida. Regardless of whether or not the traumatic origin can be deter- 
mined in detail, all of this type of pathology has as a foundation the 
cerebral congestion, edema and possible hemorrhage that has had its 
origin in the fetal asphyxia which preceded or accompanied the trauma. 

Hemorrhagic Disease of the New-Born 

While not as yet completely understood, it is now apparent that the 
condition that previously has gone under this name is common to all 
new-born. It is undiagnosable and probably is something in the nature 
of a hemorrhagic diathesis. While symptoms are caused by it in a mi- 
nority of cases, it has a high mortality, when it does cause trouble and if 
treatment is not instituted promptly. The best practice today, therefore, 
is to assume that all new-born are subject to this complication and, there- 
fore, should have, especially if not normal, an early prophylactic and 
preventive dose of parental whole blood. 

History and Symptomatology of Cranio-cerehral Injury 
of the New-Born 

In general cranio-cerebral injury of the new-born is associated most 
frequently with the first pregnancy. It has been noted, however, as a 
complication of all pregnancies up to and through the fourteenth. This 
relationship, however, is only one of a number of factors that influence 
its development. A study of the graph reproduced herewith (Fig. i) from 
an article by Clifford and Irving demonstrates at once that the occurrence 
of cranio-cerebral injury in the new-born is dependent upon a wide variety 
of factors and that its prevention is dependent upon a better understand- 

VoL. VI. 339 



136 (38) 



CRANIOCEREBRAL INJURIES 



ing and management of the whole pregnancy from the first months until 
after the umbilical cord is divided. 

In addition to the general historical background, as noted above, cer- 
tain specific data will carry additional diagnostic weight. For example, a 
story of any significant variation in the fetal heart rate, of the excessive 
administration of inhalation anesthetics to the mother or the use of mor- 
phine previous to delivery, of a primiparous or a prolonged or dry labor 
and an anomaly of the umbilical cord, all suggest the possibility of an 

CRANIO-CEREBRAL INJURIES 




ConJltloTi oitteiTifaTit atBlTta 



Fig. I. The etiological possibilities in the production of cranio-cerebral injury in the 
new-born. Reproduced from Surgery, Gynecology and Obstetrics, Vol. 65, p. 24, July, 
I937i through the courtesy of the Surgical Publishing Company of Chicago, Illinois. 



asphyxiated baby. Prolonged cyanosis, meconium in the amniotic fluid, 
difficulty in starting the baby's respiration and possibly general flaccidity 
and pallor at birth will strengthen such a supposition. Should there be, 
in addition, a history of a difificult rough labor, dystocia of the birth canal, 
bad application of forceps, delivery face to pubes or from other unfavor- 
able positions and enough pallor and flaccidity to suggest the possibility 
of surgical shock, then the physician will do well to suspect a traumatic 
type of intracranial pathology in addition to the changes that he should 
expect after asphyxia. 
Vol. VI. 339 



IN THE NEW-BORN 136 (39) 

Signs and Symptoms 

These are common to both types of intracranial injury in the new- 
born. They are present at once after birth and in all possible combina- 
tions. The commonest are hypertonicity, an abnormal or poor cry, 
cyanosis and failure to nurse. The hypertonus is best demonstrated by 
the presence of increased reflexes and more particularly by a characteristic 
excessive muscular reaction to excessive sensory stimuli. The typical ab-« 
normal cry is a sudden shriek, but it may also be absent suggesting 
unconsciousness, continuous suggesting meningeal irritation or vary in vol- 
ume, tone or frequency. Cyanosis is more frequent in the fatal cases. It 
may or may not be associated with abnormal respiration. Failure to 
nurse indicates loss of the sucking reflex and will be noticeable both when 
the baby is put to breast or given the bottle. The fontanelles usually are 
tense but by no means always. Apathy and abnormality of respiration 
are common. The latter should not be mistaken for mechanical laryngeal 
stenosis such as caused by an enlarged thymus gland. Flaccidity, pallor 
and birth asphyxia frequently appear in combination and usually are as- 
sociated with apathy, a poor cry, failure to nurse and abnormal respira- 
tion. This syndrome has been given the name of asphyxia pallida or 
pallid asphyxia. The title is descriptive but of no diagnostic value. It 
should be changed to surgical shock, since these symptoms occur in asso- 
ciation with a subnormal intracranial pressure, extensive cranial and intra- 
cranial damage and in animals, a low blood and pulse pressure. 

The intracranial pressure in the absence of surgical shock or dehydra- 
tion is increased. In the new-born it is more convenient to measure the 
cerebrospinal fluid with a mercury manometer because this type calls for 
no associated loss of fluid into the manometer. Normal pressure varies 
between 2 and 5 millimeters of mercury which is equivalent to 30 to 75 
mm. of water. Variations may extend from a high of 50 mm. of mercury 
(750 mm. water) to a low of less than i mm. of mercury (13 mm. of 
water). Puncture of the cisterna magna is unnecessary, dangerous and 
should not be practised. 

Treatment 

In general treatment is governed by the pathology as expressed in the 
diagnosis and differs in no essential from that given adults in analogous 
situations. Specifically, there are three fundamental procedures, (i) No 
active therapy other than occasional blood transfusions is permissible, 
while the patient is in surgical shock. Absolute quiet and rest with ex- 

VoL. VI. 339 



136 (4o) CRANIO-CEREBRAL INJURIES 

ternal heat and small amounts of fluid by mouth through a medicine 
dropper usually are sufficient. Blood transfusion, if done skillfully and 
without creating a disturbance or requiring movement of the baby from 
its crib, may be done, but only under such conditions. In the severe cases 
it may prove helpful to give one drachm (4 c.c.) of saturated solution of 
magnesium sulphate by rectum to be retained. (2) When the infant is 
out of surgical shock, a prophylactic transfusion of 30 to 60 c.c. of parental 
whole blood should be given. No typing or grouping is required during 
the first 10 days of life. The blood may be given into any convenient 
vein except the superior sagittal sinus. (3) The increased intracranial 
pressure must be treated now. This is done best by repeated lumbar 
punctures with removal of enough cerebrospinal fluid at each one to re- 
duce a high pressure to normal figures. Manometric pressure measure- 
ments must be made. Punctures should be repeated at least every 24 
hours until two successive normal pressures have been read previous to 
the withdrawal of any cerebrospinal fluid. The puncture requires no 
anesthesia, is best made with an adult sized needle and in any interspace 
between the 12th thoracic and the 5th lumbar. Exploratory trephination 
or the less satisfactory procedure of needle puncture of the anterior fon- 
tanelle may be resorted to provided the patient fails to improve under 
this non-operative treatment, and provided the physician wishes to rule 
out certainly the complicating presence of an expanding lesion such as a 
sub- or extra-dural hematoma. Elective operations, such as that required 
for the elevation of a depressed fracture, invariably should be postponed 
until the intracranial pressure has been reestablished at normal. 

In addition to the above specific therapeutic requirements, it will be 
well to abide by certain general rules also. These affect the baby's gen- 
eral condition and have as their object the maintenance of as nearly 
complete rest as possible together with the administration of a sufficient 
quantity of fluid and food. In the furtherance of this aim the baby should 
not be moved from the crib for any purpose whatever and should be 
handled in the crib as little as possible. Food and fluid should be given 
by a Breck feeder or gavage until the patient can take the bottle without 
danger of tiring. Fluids should be given by mouth, if possible, at the 
rate of 2 to 3 ounces per pound of weight per 24 hours. If mouth feeding 
is impossible or inadequate, salt solution should be given by clysis. If the 
rate of administration is adjusted properly and the clysis continuous, 
several hundred c.c. of fluid may be given thus into the rectum during 24 
hours. Oxygen may be given for cyanosis. Convulsions are treated best 
by lumbar punctures. Magnesium sulphate intramuscularly may be given 
in addition. Morphine in any form is contra-indicated. The effect of the 

Vol. VI. 339 



IN THE NEW-BORN 136 (41) 

relationship of the height of the feet to that of the head varies and is best 
determined by experiment. 

The Non-Opemble Intracranial Injuries of the New-Born 

The vast majority of the intracranial injuries of the new-born fall into 
this class. There are two reasons for this; first, because the pathology 
associated with asphyxia is omnipresent and as such does not require 
operative therapy and second, because the extent and severity of the re- 
sults of trauma are such that additional local trauma even though under 
the guise of a craniotomy predicates immediate death for the patient. 

Asphyxial Intracranial Injury of the New-Born 

The commonest intracranial lesion of the new-born is one that is due 
to the changes associated with asphyxia. 

Pathology. — In the early stages the pathology will vary all the way 
from cerebral congestion and edema through subcortical thromboses, pe- 
techial and coalescing hemorrhages and varying amounts of cellular and 
subcortical destruction to hemorrhages in the perineuronal, perivascular, 
subpial and subarachnoid spaces and into the cavities of the ventricles. 
If the patient survives and has been treated poorly or not at all, and in a 
certain percentage, even if the best of therapy has been provided, perma- 
nent changes result. These vary from porencephalic cysts, general or 
local cortical or subcortical atrophy or scars and cortico-meningeal ad- 
hesions to hydrocephalus ex vacuo. 

Symptoms and Signs. — These have been covered adequately in the 
preceding sections. 

Diagnosis. — The diagnosis is made from the history and the lumbar 
puncture findings. 

Treatment. — This is directed toward relieving the increased intra- 
cranial pressure. It is done by dehydration or lumbar decompression or 
both. The dehydration should be carried out in these new-born with 
considerable care, as there is a much smaller margin of safety between the 
therapeutic and the toxic varieties than there is in the adults or older 
children. It is best accomplished by the use of magnesium sulphate by 
rectum or intramuscularly. The dose by rectum is not over i drachm 
(4 cc.) of the saturated solution. It should not be repeated more than 
once and then only after 4 hours. If used intramuscularly, 7^^ minims 
{]/^ c.c.) of a sterile 50 per cent, solution is given every 3 or 4 hours. If 
the injection is made deeply into the muscle, there is little danger of 

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136 (42) CRANIOCEREBRAL INJURIES 

causing a slough. Lumbar decompression is the preferable method. This 
has been sufficiently described previously. Operation as a method of 
treatment is contra-indicated. It may be used, however, as an exploratory 
diagnostic procedure to rule out a suspected sub- or extra-dural hematoma 
after a period of non-operable therapy has failed to afford relief. It 
should be preceded usually by a trans-fontanelle subdural puncture for 
the same purpose. (See also Ratio of Occurrence and Mortality of Intra- 
cranial Hemorrhage of New-Born on a subsequent page.) 

The Inoperable Traumatic Cranial and Intracranial Injury 
in the New-Born 

The patients that fall into this group have the results of trauma super- 
imposed upon a background of pathology that is primarily due to changes 
produced by asphyxia. 

Meningeal Tears, Ruptures of Venous Sinuses, the Vein of Galen 
and the Internal Cerebral Veins 

Pathology. — Meningeal tears result from such a degree of moulding 
of the fetal head as will put an excessive strain on the tentorium or falx 
or both. The direction of the greatest deformity will determine which 
partition sustains the greatest damage. The extent of the deformity 
determines the amount of damage and the liability of involvement of 
the venous sinuses and the vein of Galen system. The simplest injury 
is represented by the harmless and avascular tears of the body of the 
falx or the splitting of the superior layer of the tentorium at its junction 
with the falx. More extensive injuries extend the tears into the superior 
sagittal, the lateral and the straight sinuses. Occurring either alone or 
in conjunction with any of the above, the vein of Galen or either or both 
of its tributaries, the internal cerebral veins, may be ruptured. These 
latter and more extensive injuries necessarily are associated with wide- 
spread and massive meningeal and ventricular hemorrhages. These may 
cover the entire surface of the cerebrum, cerebellum and brain stem and 
completely fill the entire ventricular system. 

Symptoms and Signs. — These have been adequately covered in the 
preceding sections. 

Diagnosis. — The detailed diagnosis can be made only at autopsy. It 
may be inferred from the history and the findings at lumbar puncture. 

Treatment. — The only possible and effective treatment is that which 
will care for the associated asphyxial intracranial pathology and the in- 

VoL. VI. 339 



IN THE NEW-BORN 136 (43) 

creased intracranial pressure. This has been covered above. Operations 
of any type are contra-indicated. (See also Ratio of Occurrence and 
Mortality of Intracranial Hemorrhage of New-Born on a subsequent page.) 

N on- Complicating Fractures of the Skull in the New-Born 

These fractures may involve any of the cranial bones and, as in the 
adult, are of themselves harmless. They serve only as a measure of the 
type and amount of force that has been applied to the cranium. There 
is, however, a fairly constant relationship between the etiology and the 
location of the break. Misapplication of forceps will produce eggshell 
fractures at the point or points that correspond to the tips of the blades. 
Traction of the head through forceps, however applied, plus a combina- 
tion of bending and twisting the neck as in the Scanzoni maneuver will 
cause a fracture of the base of the skull that usually includes the foramen 
magnum and is complicated by a broken neck. 

Pathology. — The pathology in addition to that produced by the as- 
sociated asphyxia is adequately described in the one instance as an egg- 
shell fracture of a fiat bone and in the other as a comminuted or linear 
fracture in or near the foramen magnum. 

Signs and Symptoms. — These have been described adequately above. 

Diagnosis. — The diagnosis is made on the history and lumbar punc- 
ture findings and at autopsy. 

Treatment. — The only effective and possible treatment is that directed 
toward correcting the results of the associated pathology that has followed 
the accompanying asphyxia. This has been discussed sufficiently above. 
It is in these cases that prophylaxis proves to be the best therapy. (See 
also Ratio of Occurrence and Mortality of Intracranial Hemorrliage of 
New-Born on a subsequent page.) 

The Operable Cranial and Intracranial Injuries of the New-Born 

The operable cranial and intracranial injuries in the new-born are 
made up of the expanding meningeal hemorrhages and the depressed 
fractures. Both are present in addition to the pathology that is produced 
because of asphyxia. 

Subdural Hematoma 

Pathology. — Subdural hematomas in the new-born, as far as is known 
at present, are due to the rupture of a bridging vein where it crosses the 
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136 (44) CRANIO-CEREBRAL INJURIES 

subdural space on its way from the cortex to a major venous sinus or 
its adjacent dura. They may be associated with either the asphyxial or 
the traumatic type of etiology. The veins, which are almost always 
cerebral, rupture because they are congested and distended, their ex- 
tensibility is gone and hence, when moulding and over-riding at an 
adjacent suture line takes place, they are unable to compensate for it by 
elongation and so break. The bleeding end empties into the subdural 
space and produces a solid subdural hematoma. Because there is no 
associated tear in the arachnoid and hence no admixture of cerebrospinal 
fluid, these hematomas are made up exclusively of blood. Their content 
is, therefore, at first fluid, then clot with a fluid centre and surrounded 
by organizing membranes and finally yellow fluid with a high protein 
content contained within a thick-walled fibrous cyst or as represented 
by a complete fibrous organization. They are expansile only during 
their formation. They may, therefore, be present for periods of months 
or years without causing any demonstrable alteration in intracranial 
pressure, room being provided within the cranium by a local atrophy of 
the underlying cortex. 

Symptoms and Signs. — The symptoms and signs are those of the 
associated asphyxial pathology and have been adequately discussed pre- 
viously. In addition there is some reason to suppose that, as a result 
of the presence of the clot, there is in all probability a greater liability 
on the part of the patient to have a hemiplegia and/or to develop convulsive 
attacks. 

Diagnosis. — The diagnosis can be made only by exploratory trephina- 
tion or subdural puncture through the anterior fontanelle. One, or if 
necessary, both of these procedures should be employed always whenever 
the infant fails to improve under properly applied non-operative therapy 
which has been, up to that point, based on a diagnosis of either asphyxial 
or traumatic cerebral edema or subarachnoid hemorrhage. They should 
not be delayed unduly. 

Treatment. — Treatment is operative. If there are good and sufficient 
reasons for it, an attempt may be made to evacuate the hematoma by 
repeated subdural punctures through the anterior fontanelle. There is 
today, however, a considerable accumulation of experience which makes 
it probable that no better than partial evacuation at the best can be ex- 
pected from this method. Trans-temporal trephination, if necessary bi- 
lateral, with evacuation of the hematoma under the direct view of the 
operator is the procedure of choice for these cases. (See also Ratio of 
Occurrence and Mortality of Intracranial Hemorrhage of New-Born on a 
subsequent page.) 

Vol. VI. 339 



IN THE NEW-BORN 136 (45) 

Extradural Hematoma 

This is an uncommon lesion in the new-born except as one of a num- 
ber of severe associated cranial injuries. Probably it has never been diag- 
nosed during life except by accident. 

Pathology. — The source of the clot usually is found in multiple rup- 
tures of the terminal twigs of the middle meningeal artery. These vessels 
tear at points where they perforate the inner table of the skull to act as 
nutrient vessels for the bones or to continue through the diploe and outer 
table to anastomose with one of the scalp arteries. They are associated 
with eggshell fractures of the temporal, parietal or frontal bones. Other 
sources are a rupture of one of the cranial venous sinuses in association 
with other and more extensive injuries or, a surgical curiosity, a rupture 
of the trunk or one of the main branches of one of the middle meningeal 
arteries. Since in the new-born the dura is continuous through the suture 
lines with the periosteum, the size of the extradural clot necessarily is 
limited by the size of the bone that it underlies and the elasticity of the 
dura. Its effect on the brain is localized correspondingly. 

Signs and Symptoms. — These are not clear. Whatever specific pecu- 
liarities exist as the result of this condition are in addition to those due to 
the associated brain lesion. These latter have been discussed sufficiently 
in previous sections. There is no tri-partite pathognomonic history as in 
the adult. Convulsions, a persistent or increasing hemiplegia, a high, ir- 
reduceable intracranial pressure and tense fontanelles ought to be asso- 
ciated frequently with this condition. 

Diagnosis. — This can be made only by exploratory trephination. 

Treatment. — This is surgical. It should include evacuation of the clot, 
closure of the bleeding artery or arteries by ligation or some similar 
method and a subtemporal decompression. The Ratio of Occurrence and 
the Mortality are unknown. 

Depressed Fracture of the Skull 

Pathology. — This lesion usually is caused by pressure of the baby's 
head against the promontory of the sacrum or the symphysis pubis. 
It may be caused also by the misapplication of forceps. Any bone may 
be involved. The lesion is a characteristic "celluloid ball" depression 
without a fracture. Mild degrees of asphyxial intracranial damage usually 
are associated with it. 

Symptoms and Signs. — These are for the most part covered above. 
The special sign that goes with this fracture is a spoon-shaped depression 

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136 (46) CRANIO-CEREBRAL INJURIES 

in the injured bone. It is both visible and palpable and has little or no 
hematoma around it. 

Diagnosis. — The diagnosis is made from the visible and palpable find- 
ings on the skull. X-rays are of little help. 

Treatment. — This is exclusively operative in as much as these de- 
pressions do not elevate themselves. The procedure should be formal and 
one that will permit of an elevation under direct vision in order to avoid 
causing cortical or meningeal damage. Elevation by means of a sharp 
hook which is used first to perforate the scalp and bone and then to jerk 
the depression into place is inexcusable. After proper elevation the de- 
pression will not fall back. The operation should never be undertaken 
except as a procedure of choice and only then after repeated lumbar 
punctures have made it certain that the associated asphyxial cerebral 
pathology is righted and the intracranial pressure again established per- 
manently at normal. Of itself, and provided it is properly treated, this 
lesion should carry no mortality. Any bony defect will fill in. Under 
other circumstances, the statements made under Ratio of Occurrence and 
Mortality of Intracranial Hemorrhage of New-Born on a subsequent page 
will apply. 

Complications of Cranial and Intracranial Injuries of New-Born 

Predictable complications of cranial and intracranial injuries of the 
new-born, while not as common as in the similar adult injuries, do occur 
sufficiently often to merit discussion. Their mathematical incidence is 
not known. They include surgical shock, toxic dehydration, intra-uterine 
and post-partum infection of the central nervous system and injuries to 
the soft tissues of the face and scalp. 

Surgical Shock 

This can be made only as a presumptive diagnosis at present. Proof 
of its presence in any given case will be lacking because of the imprac- 
ticability of measuring blood pressures on these infants. However, even 
in the absence of this final proof, the presumptive evidence is so strong 
and its diagnostic importance so great that its presence from the prac- 
tical point of view should be assumed. 

Diagnosis. — If a baby, that is known to have been seriously battered 
and injured about the head during the course of labor or delivery, is pale, 
flaccid, unconscious and cyanotic at birth, if its temperature is subnormal, 
its intracranial pressure the same, and if it bears ample external evidence 

Vol. VI. 339 



IN THE NEW-BORN 136 (47) 

of having been severely traumatized, the diagnosis of surgical shock 
should be made. A presumptive diagnosis of the same condition should 
be made also on the objective findings listed above and even in the ab- 
sence of a traumatic history or in the presence of an asphyxial one. 

Treatment. — The prime requisite of treatment is absolute rest and 
quiet with sufficient fluids internally and heat externally. Blood trans- 
fusion, if it can be done without moving the baby at all, will be helpful. 
(See also Ratio of Occurrence and Mortality of Intracranial Hemorrhage of 
New-Born on a subsequent page.) 

Toxic Dehydration 

This condition in the new-born is exactly like that in the adult. It 
arises from the same causes, overheating including fever, insufficient fluid 
intake, diarrhea and vomiting; it mimics or reproduces the symptoms 
of increased intracranial pressure; it is characterized by sunken fon- 
tanelles, low intracranial pressure, dry shrunken skin that has lost its 
elasticity, and fever; the hematocrit reading of the blood may be ex- 
tremely high, and it is cured by the administration of sufficient fluids to 
produce hydration. Hydration usually will require an intake of from 30 
to 60 c.c. of total fluid per J^ kilo (2.34 pounds) of body weight during 
each 24-hour period. It can be given by mouth or by constant drip clysis. 

Ratio of Occurrence. — This is not known but probably is high. 

Mortality. — If the condition is unrecognized and, therefore, not 
treated, this is high. 

Central Nervous System Infection 

An infection that is directly attributable to the cranio-cerebral injury 
itself is rare but by no means unknown. It is in the form of the classical 
purulent meningitis. Treatment is ineffective although sulphanilamide 
may be tried. Mortality is 100 per cent. 

Fetal Meningitis has occurred once in my experience. The disease ran 
its full course before delivery, and the diagnosis was made only by the 
microscopic appearance of the brain and meninges. 

Contusions of the Face and Scalp, Cephalhematomas and Caput 

Succedaneum 

Contusions of the face and scalp may be produced either in the natural 
course of labor or by the misapplication of forceps. They may include 
Vol. VI. 339 



136 (48) CRANIO-CEREBRAL INJURIES 

the eye and ear. They are of little consequence unless one of the facial 
nerves has been damaged. Under such circumstances particular care 
should be given the eye. Complete interruption of the nerve in front of 
the ear can occur but is rare. It has been recommended that, if such a 
condition is present, and there is in addition a complicating overlying 
tear of the skin of the face, the facial nerve should be explored at once 
and sutured if need be. 

Cephalhematomas are subperiosteal hemorrhages. As such, after two 
weeks, enough bone may be laid down in the lateral wall to give a sensa- 
tion of crackling when the hematoma is palpated. Such bone formation 
never proceeds beyond this point, however. The bleeding is limited by 
the periosteo-dural attachments through the suture lines and by the un- 
derlying bone. Though the hematoma may spread laterally over more 
than one bone, it will not enter the cranial cavity and can have no effect 
upon the cranial content. Rarely, in the very large ones, enough blood 
may be lost into it to cause an anemia for which transfusion will be indi- 
cated. 

Treatment. — The important thing about treatment is, except in the 
rare emergency of an enormous clot, to leave them completely alone. In 
particular they should not be needled, incised or drained. They will take 
care of themselves eventually by absorption. Invasion of the clot leads 
to infection in almost every instance. This is more important in the new- 
born than in the adult because, due to the vascular connections in the 
former, sepsis of the scalp is particularly apt to cause osteomyelitis of the 
skull. 

Caput Siiccedaneum. — This is an instance of localized subgaleal 
edema. As such, it requires no treatment and in particular should not 
be needled, incised or drained because of the unnecessary and great risk 
of infection. 

Ratio of Occurrence and Mortality of Intracranial Hemorrhage 

of New-Born 

Those figures that are available give the ratio of occurrence of intra- 
cranial hemorrhage in the new-born as varying from 44 per cent, in post- 
mortem series to from 2 to 6 per cent, as obtained from clinical studies. 

The immediate mortality can only be approximated. It is probably 
somewhere in the neighborhood of 50 per cent. The development of late 
symptoms that are primarily due to changes originally caused by the 
birth injury necessarily depends upon the accuracy of the original diag- 
nosis and the efificiency of the treatment in any given case. In one series 

Vol. VI. 339 



FIRST AID 136 (49) 

of cases followed for 7 years hydrocephalus associated with epilepsy or 
idiocy was the commonest of the unfavorable end results, although con- 
vulsions alone and spasticity associated with idiocy also occurred. Fifteen 
per cent, of this group had such late symptoms. Other smaller series that 
were studied independently yielded the same figure. It is probable, how- 
ever, that this figure is much too low for the population at large, since it 
is unlikely that the average new-born baby is studied and treated as care- 
fully as those in these special series were. 

First Aid in Cranio- Cerebral Injuries 

Successful first aid or emergency care of patients with cranio-cerebral 
injuries requires from the doctor the answer to three questions. If these 
are answered correctly and intelligently, the ultimate mortality and mor- 
bidity will be reduced, and later necessary surgical procedures will be 
simplified with all the benefit to the patient that that implies. These 
questions are (i) Is the patient in surgical shock? (2) Is the injury one 
that will require treatment by operation within the next 48 hours and, if 
so, is the hospital in which he is being examined adequately equipped to 
handle such a procedure? (3) What is the intracranial pressure and how 
much blood does the cerebrospinal fluid contain ? 

75 the patient in surgical shock ? — To determine this it is only necessary 
to measure his systolic and diastolic blood pressures. However, before 
proceeding to that, it is well for the physician to consider the suitability 
of the patient's surroundings. If, for example, he is first seen lying out in 
the road, a decision must be reached as to whether or not he should be 
moved under cover first. This decision should be affirmative providing 
the transportation is limited solely to that requisite to get him under 
cover. Only in this way can unjustified exposure to cold with its increase 
in shock or to heat with its excessive dehydration be avoided. Such move- 
ment, in addition to being minimal, should be made with due regard to 
any other injuries and in a horizontal position. With sufficient help the 
patient can be moved safely by using his overcoat, which is adequate 
support providing an assistant is assigned to handle the head only. This 
will eliminate the double moving required whenever a stretcher is used. 
It makes no particular difference what kind of a shelter is used, provided 
that it is warm or cool as the weather requires. If, however, a proper 
ambulance is available, and there is room for the patient to lie flat in it, 
there is little added risk in a 20-minute or half-hour drive to the nearest 
hospital. This holds particularly true if that institution is adequately 
equipped to care for this type of emergency. 

Vol. VI. 339 



136 (5o) CRANIO-CEREBRAL INJURIES 

With the patient indoors it is the physician's first responsibiHty to see 
to it that his clothes are not removed. Such manipulation in the presence 
of surgical shock may prove all that is necessary to precipitate a fatality. 
Furthermore, from a diagnostic point of view such a procedure is of no 
conceivable use. The objection will be raised that with the clothes still 
in place, the presence of coat or dress sleeves will interfere with the use 
of a sphygmomanometer and the presence of a trouser leg with the treat- 
ment of associated injuries of the lower extremities. These objections are 
met adequately and best by slitting the sleeve along the seams and by 
the application of splints and bandages either over the trouser leg and 
shoes or directly to the skin after the former has been slit up the seams 
also. Adequate chest and abdominal examinations, if they cannot be 
postponed until after blood pressure readings are available, can be made 
through the loosened clothes, their complete removal being superfluous at 
this time. 

In any event systolic and diastolic blood pressures should now be 
measured. If the difference between the systolic and diastolic readings, 
the pulse pressure, is 15 mm. of mercury or lower, it may be taken for 
granted that the patient is in shock. If it is 20 mm. of mercury or above, 
a second observation must be made at the end of 30 minutes; if, at the 
end of that period, the systolic pressure has fallen or the pulse pressure 
decreased, the diagnosis of surgical shock again is obligatory. Should 
either or both of these pressures show an increase, surgical shock may be 
considered as being absent. If there is no change, a third and check read- 
ing should be made at the end of another 30 minutes. 

If thus it has been determined that the patient is in surgical shock, 
then all further examinations, any projected transportation and all therapy 
except for the splinting of broken bones and the treatment of the shock 
must be abandoned for the time being. Since in the usual case of cranio- 
cerebral injury an adequate supply of properly cross-matched compatible 
blood practically is never available, any hope for the ideal treatment by 
blood transfusion must be given up. As a substitute, however, 50 per 
cent, glucose solution may be given intravenously. This is stocked by 
almost every drug store in 50 c.c. sterile ampoules. The adult dose is 
one or two such ampoules given undiluted. Care must be taken to see 
that the solution does not get into the perivenous tissues, as its presence 
outside of the lumen of a vein is liable to cause local sloughing. The dose 
may be repeated in 2 hours if necessary. Salt solution should never be 
given in the treatment of surgical shock. Other therapy includes seeing 
to it that the patient is kept warm but not overheated, has all broken 
bones properly splinted, does not receive morphine or any of its deriva- 

VoL. VI. 339 



FIRST AID 136 (51) 

tives, has fluids by mouth in small amounts if conscious, empties his 
bladder, if necessary and able to do so, and above all is kept completely 
quiet and not exposed to bright light, insurance adjusters, anxious rela- 
tives and police. His head should be kept lower than or on a level with 
his pelvis unless a complicating chest injury necessitates elevation. In 
this way, the physician obtains his answer to the first question of "Is the 
patient in surgical shock?", and deals with it appropriately. 

Is the injury one that will require treatment by operation within the next 
48 hours? — The reply to this first part of the second question that the 
physician must answer will be in the affirmative as far as the cranio- 
cerebral injury goes, only if one of three diagnoses can be made or cannot 
be ruled out. The first and most important of these diagnoses is that of 
an extradural hemorrhage. The mere suspicion or the probable demonstra- 
tion of the presence of such a lesion makes it imperative to have the pa- 
tient in an institution equipped to deal with this major emergency. This 
requirement well may imply transportation for some distance. Such a 
diagnosis, at least as a possibility, must be made as soon as can be, in 
order that the movement of the patient will have been completed before 
he is too sick to permit of any help by operation. At the time of the 
injury the diagnosis is made best from the history. It should be obtained 
as accurately as possible and in full detail from the witnesses. In par- 
ticular, if the patient is conscious when first seen, the greatest care must 
be taken to determine the presence or absence of any antecedent period of 
unconsciousness. 

If the patient can be suspected justly of harboring an extradural clot, 
he must be moved at the earliest possible moment to a hospital equipped 
with satisfactory staff", operating room personnel, instruments, mechanical 
aids and available grouped blood donors. Within limits the distance to be 
covered is of no importance in the face of avoiding the tragic necessity of 
having to do a major operation of this type in an inadequately equipped 
operating room with untrained or poorly trained staff and no donors. After 
arrival at the selected institution any further procedures necessary to con- 
firm the diagnosis and the necessity for operation can be carried out there. 
These may well include a neurological examination, a lumbar puncture with 
measurements of the cerebrospinal fluid pressure, a single x-ray plate and 
so forth. 

If, on the other hand, the physician decides that his patient is not 
suffering from an extradural hemorrhage, he must then proceed to ascer- 
tain the presence or absence of the second condition that requires opera- 
tive therapy within the next 48 hours. This lesion is a compound fracture 
of the skull. Any patient with a scalp wound has a potential fracture of 

Vol. VI. 339 



136 (52) CRANIO-CEREBRAL INJURIES 

the skull. The first examination then will be to determine whether or 
not a scalp wound is present. If there is no scalp wound, there can be 
no compound fracture of the skull unless it be through the posterior wall 
of a frontal sinus, a condition that does not constitute an emergency. If 
there is a scalp wound, the additional presence of a fracture beneath it, 
which is compounded by its presence, is best determined by palpation 
through the wound with one's sterile finger. Compounding will be present 
only if the soft tissues, including the periosteum, are torn over the fracture 
line. Instruments and other means for examining the wound should not 
be substituted for the examiner's finger except in the rarest instance. The 
scalp should not be cleansed, the hair should be left uncut, and in particular 
the wound must not be irrigated or flooded previous to the palpation. If 
it can be demonstrated that there is a fracture line and that it is com- 
pounded, nothing, literally nothing, further should be done at this time 
except to cover the wound with a sterile piece of gauze and a bandage, 
neither of which should be removed until the patient is anesthetized and 
on the operating table being prepared for a debridement. Compound 
fractures of the skull require for their proper treatment the same type 
and amount of equipment and personnel that an extradural clot does. 
That patient, therefore, that has such a fracture is safer if he is moved 
than if he is subjected to surgery in a hospital that cannot meet such 
standards. He does not have to be moved, however, as soon as would be 
required for the treatment of an extradural hemorrhage. Compound 
fractures need not be debrided within the first 24 hours after their receipt, 
providing the wound is not manipulated in any way. Prophylactic ad- 
ministration of sulphanilamide may be started and continued until the 
necessity for its use has been confirmed by wound cultures. On the other 
hand debridement must be completed within 48 hours after the receipt of 
the injury, if the surgeon is to keep the patient's chance of morbidity 
from sepsis down to the proper level of 5 per cent. The transportation 
of the patient with a compound fracture of the skull should be carried out 
after he is out of surgical shock but soon enough after so that he can have 
some time to rest at the new hospital before being operated upon and 
before the 48-hour period has expired. 

In the absence of both an extradural hemorrhage and a compound 
fracture of the skull, the only other condition that requires operation 
within 48 hours after receipt of the accident is the condition that is mani- 
fested by the escape of cerebrospinal fluid from the nose. Cerebrospinal 
rhinorrhea is caused by a fracture into the nose through the cribriform 
plate, one of the ethmoid cells or one of the frontal sinuses. Thus, it is a 
compound fracture with the compounding into the nasal cavity rather 

Vol. VI. 339 



FIRST AID 136 (53) 

than through the scalp. The flow of cerebrospinal fluid occurs because a 
funnel of dura and contained arachnoid has been caught and held in the 
fracture line. The smaller end of this funnel lies in the nose and thus 
directly connects this cavity with the meningeal spaces. It further per- 
mits a stream of cerebrospinal fluid to flow constantly from the latter into 
the former. The diagnosis is made by the demonstration of cerebrospinal 
fluid either alone, or, at this time more usually mixed with blood, dripping 
from the nostril or into the posterior nasopharynx. The latter flow will 
be recognizable and will come from the nostril when the patient's head is 
raised. The necessity for transportation, the need for surgery and the 
indication for the administration of sulphanilamide in this condition are 
the same in every detail as that described above for compound fracture 
of the skull. Only one variation exists. That lies in the infinitely greater 
technical difficulty attendant on this operation as compared to that of 
the ordinary compound fracture of the skull. 

Thus, by virtue of an adequate history, the proper examination of the 
scalp and scalp wounds and observation of the type and amount of nasal 
discharge in a patient, who has just received a cranio-cerebral injury, one 
can determine the answer to the second question. This will enable the 
physician to decide whether or not this particular case should be operated 
upon within the next 48 hours. A further decision as to the need for 
transportation will depend upon the facilities available at the institution 
where the patient is seen first. 

What is the intracranial pressure and how much blood does the cerebro- 
spinal fluid contain? This third question can now properly be considered. 
As the answer to this question obviously is to be made by way of a lum- 
bar puncture, it will be necessary to undress the patient at least partially. 
Since this is so, and since there is no more fuss about completely undress- 
ing a person than there is about partially doing so, and since if that is 
done, he should be in bed and preferably in a bed where he is to remain 
permanently, it is well to postpone the answer to this third question until 
it has been settled where he is to be cared for. This should never, in 
these cases, be at home. If the choice involves transportation for any 
distance up to 250 miles, and provided the ambulance is modern and 
the roads good, or adequate train accommodation available, he can be 
moved with perfect safety at this time as far as his cranio-cerebral injury 
is concerned. Local conditions will govern the physician's decision to do 
a lumbar puncture before the transfer. As a method of temporizing hyper- 
tonic glucose always can be given intravenously at this time and the lum- 
bar puncture done later on. Wherever the patient is finally hospitalized, 
however, it is now that his clothes are removed for the first time. Coin- 

VoL. VI. 339 



136 (54) CRANIO-CEREBRAL INJURIES 

cidently with this, physical and neurological examinations should be done. 
Steps can be taken to treat temporarily any associated injuries. An 
estimation of the amount of cerebral injury can be made and a decision 
reached about the possibility of permanent therapy for the former and 
their mutual effects upon each other evaluated. A more complete history 
can be obtained also, especially as regards the possibility of dehydration. 
Lumbar punctures must give data in regard to the cerebrospinal fluid 
pressure, the amount of fluid that had to be removed to reduce a high 
pressure to normal, the amount of macroscopic blood contained in it and 
the degree of relaxation of the patient. Taken in conjunction with his 
knowledge about the presence or absence of surgical shock and the possi- 
bility of dehydration, the physician now should be able to determine from 
this data what type of fundamental cerebral pathology is present. Having 
made this distinction and set it down as concussion, edema and conges- 
tion, or contusion and/or laceration of the brain and having ruled out 
compound fracture and an extradural hemorrhage, the emergency, as 
far as therapy goes, is ended. Furthermore, he has built himself a firm 
diagnostic foundation upon which he can later, if the welfare of his patient 
requires it, erect a superstructure of x-ray examinations, repeated lumbar 
punctures, exploratory trephinations and other procedures necessary to 
complete in every detail the diagnostic picture of the patient's injury. 

Convalescent Care of Cranio-Cerebral Injuries 

Regardless of the type of injury or the details of the cerebral or bony 
damage all patients that have sustained a cranio-cerebral injury should 
have their convalescence supervised by a physician. He is the only one 
that is sufficiently detached from the emotional and legal points of view 
to protect the patient from the psychological assaults of lugubrious friends 
and relatives and the effects of over-developed self-interest as fostered by 
lawyers, insurance adjusters and the like. 

It has been the custom to tell these patients to go home and rest up 
for periods ranging from a few weeks to many months after their discharge 
from the hospital. Usually the advice is purely empirical, and its effects 
are correspondingly variable and unsatisfactory. Analytical study of any 
cranio-cerebral injury will demonstrate that, in essence, the acute phase 
differs in no way from that associated with the healing of any wound. 
It is not commonly considered in that light because the wound usually is 
invisible, its progress toward recovery cannot be watched, and the diag- 
nosis usually does not serve as a word-guide to the pathology. The va- 
rious procedures described in the foregoing sections have to do with the 

Vol. VI. 339 



CONVALESCENT CARE 136 (55) 

means for treating the tissues of the skull and brain in such a way that 
this wound healing can take place under the optimum conditions. Hemor- 
rhage is controlled, expanding or space-occupying clots are removed, the 
intracranial circulation is restored to normal, and infection is combated or 
prevented. These requisites having been fulfilled, normal healing will 
progress and cicatrization take place in accordance with the same laws 
that govern tissue repair in other and more visible parts of the body. 
What variation there is will be found in the inability of the nervous tissue 
to reproduce destroyed cells and in the difficulty with which the flat cra- 
nial bones fill defects that have been created in them. Insofar then as 
these peculiar deficiencies cause destruction, and regardless of the wound 
healing, there will result permanent functional loss that is irreparable. 
Such local peculiarities, however, do not alter the underlying situation. 
Since repair of wounds depends upon the integrity of the blood supply 
and the efficiency of the oxygenation of the damaged tissues, the final 
stages of wound healing that lead to permanent cicatrization begin when 
the circulation has returned to normal, provided only that infection does 
not complicate the picture. Because of their interdependence, this phase 
starts in cerebral wounds with the return to normal of the intracranial 
pressure and its stabilization at that level. It is at this point that the 
patient's convalescent period begins, and it is from these facts that the 
starting date is determined. 

The First Period of the Convalescence 

This period is devoted to making certain that the various cranio- 
cerebral wounds heal as completely and rapidly as possible. To facilitate 
that and because it lessens the extraneous demands on the patient's 
metabolism and circulation, the patient is kept flat in bed during it. If 
infection is not present, any wound should be healed solidly in 10 days, 
especially if the patient is allowed no activity. To be on the safe side, 
however, this time is extended for 4 more days and the patient kept flat 
in bed for 2 weeks from the date his intracranial pressure has returned to, 
and become stabilized at, normal. At the end of that time he is allowed 
to get out of bed and to start the second phase of his convalescence. 
Appropriate adjustments are made for infected wounds. 

The Second Period of the Convalescence 

This second period is devoted to getting the patient into such good 
general condition that he can leave the hospital for his home without the 
Vol. VI. 339 



136 (56) CRANIO-CEREBRAL INJURIES 

necessity of being invalided at the latter place. Because of the traditional 
mystery associated in the mind of the ordinary layman with brain in- 
juries and the fear of insanity that besets the victim of such accidents, 
these patients will be particularly apt to use the doctor's directions in- 
stead of their own initiative when they are faced with a situation that 
requires the assumption of responsibility. They are thus provided with 
a perfect alibi for the development of any later symptoms. These alibis 
will metamorphose shortly into mechanisms whereby the patient is able 
to avoid the performances of unpleasant tasks, such as earning a living, 
or will serve to rationalize symptomatology that has only a psychotic 
background. The development of a neurosis is particularly apt to occur 
later, therefore, unless properly forestalled at this early period. This 
forestalling process is started most easily and most efficiently when the 
time comes to get the patient out of bed. Its essential underlying prin- 
ciple is that the patient shall be kept continually in a position where he 
is asking to be more active than the doctor is apparently willing to allow. 
As a result, he will, in spite of himself, assume the responsibility for all 
his actions and, therefore, the symptoms that may arise out of them. In 
this way any invalidism that he develops will be of his own creation and 
thus cannot be used as a means of avoiding his inevitable physical re- 
covery. 

The first step is taken when the physician, not the nurse or the interne, 
tells the patient that he can now get out of bed. When he asks for how 
long a period, he should be told to stay up until he is tired, after which 
he is to get back into bed again, rest and then get up again. Great care 
is taken to see to it that no time limit is set and that his "gettings up and 
his lyings down" are governed completely and solely by his own initiative. 
No further directions are given until he asks when he can go home, al- 
though such remarks as will tend to shame a slow, timid patient into 
greater speed should not be omitted. This date is determined by his 
demonstration while at the hospital that he is no longer invalided, and the 
question is answered specifically by telling him that he can go home after 
he has been up and down two flights of stairs twice in succession. The 
patient, who can do this in the hospital as the price of going home, can 
not in justice to himself become an invalid in the bosom of his family. 
In particular, he can not justifiably ask for breakfast in bed at home and, 
when once up and about the house at the same time as and with the 
family, he must, to save his face and because the situation is one of his 
own making, continue active for the rest of the day. 

When he has demonstrated thus that he is ready and able to go home 
and be active, he and his immediate family are told in detail about any 

Vol. VI. 339 



CONVALESCENT CARE 136 (57) 

permanent disabilities that have resulted from the injury. A prognosis is 
given them relative to this phase only, they are cautioned against over- 
solicitous neighbors, and it is impressed upon them that the patient has 
demonstrated of his own volition that he is capable of being amenable 
to family discipline. It is then explained that except for the permanent 
disability, already mentioned, they may look upon the cranio-cerebral 
injury as having been completely cured and that, therefore, all that the 
patient h"as to do now is to build up his general condition by his own ef- 
forts until he reaches that degree of strength and activity that he had 
before the accident. 

The Third Period of Convalescence 

The third period of convalescence, if the foundation has been built 
up as described during the first two, concerns the patient's general health. 
Any modification has to do only with those rare special procedures that 
are called for by the presence of the permanent disabilities noted above. 
This, however, does not alter from a practical point of view the truth 
of the preceding statement. From the physician's angle the problem now 
is the same as that which characterizes invalidism after any serious illness 
such as pneumonia or a major abdominal operation, except that it is 
simpler. In handling it the patient must be made to assume again the 
initiative. Success is not always attainable and varies directly with the 
degree of intelligence of the patient. In any event the maximum time 
that should be allowed for complete return to normality within the 
limits of the permanent disabilities should not exceed three months from 
the dateW leaving the hospital. Patients, who have had diagnoses and 
therapy based upon adequate demonstration of the pathology present, 
and whose previous convalescence has been directed as above, but who 
are not back to normal life by that time, should be dismissed as per- 
manent invalids, and their families told to make arrangements to care 
for them as such. It is only in these cases that a diagnosis of post- 
traumatic neurosis properly can be made, and only then if an explora- 
tory transtemporal trephinement has been included among the earlier 
diagnostic procedures. 

Every physician will have his own particular methods for building up 
his patient's general health. Provided that the underlying principle that 
requires the patient to assume full responsibility for his own actions and 
to depend upon his own initiative for his speed of recovery is recognized, 
it makes little difference what the details of treatment are. I have had 
most success with industrial cases, however, when the patient has been 

Vol. VI. 339 



136 (58) CRANIO-CEREBRAL INJURIES 

allowed to put himself back to work on a part-time basis before under- 
taking a full time job again. This, of course, requires a type of coopera- 
tion from the employers that the doctor may not be able to get. In 
general all such patients must understand in detail what their permanent 
disabilities are to be, and they must be forced to govern their own rate 
of recovery by their own actions. Absolute prohibitions are as follows: 
they must give up all alcohol for the rest of their lives; they should not 
dive head-first into water, nor should they go onto high places that are 
not sufBciently protected to keep them from falling ofif in case they get 
faint. The danger of fainting applies also to the prohibition against 
diving. Obviously, if this happens while under water, drowning will 
result. Alcohol is prohibited because experience has shown that its 
ingestion after cerebral injury predisposes to or else wall produce con- 
vulsive seizures. 

"The Chronic Post-Traumatic Neurotic" 

The patient, who is commonly spoken of as having post-traumatic 
neurosis, compensation neurosis or malingering after a claimed injury to 
the head, usually comes to the physician for relief at least a month and 
often years after the original injury. His complaints practically always 
are subjective rather than objective, and his morale usually is very low. 
Furthermore, his outlook often is prejudiced by pending litigation or 
some similar emotional application. Not infrequently he will have been 
sent by an insurance company or lawyer for an opinion as to the genuine- 
ness of his symptoms. 

Since such patients almost never go back to their original doctor for 
advice about their late symptomatology, the physician who sees them at 
this later date is forced to start his investigation with a review of the 
original condition. He should, therefore, determine first of all whether 
or not the patient did actually receive a head injury as he claims. Head- 
aches, postural dizziness and tinnitus has been shown to occur as the only 
symptom in 71, 64 and 45 per cent, of this group, and the presence of any 
one of these symptoms is strong presumptive evidence in favor of the 
patient's claim. 

Confirmation may be had from the history. This should be factual 
and in the nature of a cross-examination. If unconsciousness, amnesia 
before or after the accident and /or headaches after return to consciousness 
can be shown to have been present, the doctor may conclude that the 
patient did in fact injure his head as claimed and may, therefore, be 
having late symptoms that are due to this old injury. A scar on the head 
Vol. VI. 339 



CONVALESCENT CARE 136 (59) 

and appropriate x-ray findings will ofifer further confirmation provided one 
can be sure that they were caused by the injury in question. 

This is the ultimate that can be done with an office examination. An 
opinion, that is based on such an examination and that states more than 
the bare fact that the patient probably did have a cranio-cerebral injury 
as claimed and that this is an adequate cause for his present late symp- 
toms, or that the patient did not have a head injury as claimed and that, 
therefore, his late symptoms cannot be ascribed to such a cause, is in- 
accurate and cannot be backed up by facts. Further diagnostic, thera- 
peutic and prognostic details must await hospitalization of the patient. 

If this is consented to, the investigation again must be primarily fac- 
tual. Ordinary hospitalization should serve to identify the presence of a 
previously unrecognized intercurrent physical or mental disease, an ex- 
panding intracranial lesion, such chronic diseases as multiple sclerosis, 
syphilis, arteriosclerosis, syringomyelia, pernicious anemia, other blood 
disease, disease of the kidneys, local bone injury and the like. Studies 
should include general physical and neurological examinations, the making 
of special mental tests, tests of the special senses, study of the blood and 
urine, lumbar puncture with an estimation of the intracranial pressure and 
chemical, serologic and cytologic examinations of the cerebrospinal fluid 
and adequate x-ray examination. These all demonstrate objective facts 
and constitute the minimum that must be done to allow an inferential 
opinion as to the physical relationship between the accident in the past 
and the subject's symptomatology of the present. If all examinations are 
negative, the only report that can be given is to the effect that the patient 
at this time shows no objective evidence of disease and that he either did 
or did not have a previous head injury, as determined from the history, 
and that, therefore, his present symptoms may still be due to neurosis, 
malingering, a subdural hematoma, cerebral atrophy or psychotic mal- 
adjustment. 

If further information is desired, either for purposes of accuracy or to 
initiate therapy, the indications for which are not already apparent, the 
patient must submit himself to either encephalography or exploratory 
trans-temporal trephination. 

Encephalography can be expected to demonstrate cortical atrophy 
with a high degree of accuracy, solid subdural hematomas sufficiently 
often to be a valuable adjunct in diagnosing them and fluid subdural 
hematomas and encysted fluid not at all. It should be noted that none 
of these conditions need be accompanied by any objective changes that 
would, necessarily, be demonstrable by any of the procedures discussed 
above. Encephalography has no value as a method of treating the sub- 

VoL. VI. 339 



136 (6o) CRANIO-CEREBRAL INJURIES 

jective symptoms which lead to the examination. Since there is a minimal 
but definite risk attached to the procedure, specific written permission for 
its performance should be obtained from the patient or his legal represen- 
tatives before carrying it out. 

The final diagnostic procedure is trans-temporal trephination. This 
supplements encephalography and is the only way in which the presence 
of a fluid subdural hematoma can be recognized short of a guess. It will, 
at times, also serve to establish the presence of associated non-traumatic 
conditions that have been missed by the other examinations. Fluid sub- 
dural hematomas are a more frequent cause of subjective, symptoms after 
cranio-cerebral injuries than is commonly supposed. Exploratory tre- 
phination should be offered to every one of these chronic invalids for that 
reason alone. However, because it is essentially and primarily diagnostic, 
the offer should be qualified in such cases with the statement that no 
guarantee is either given or implied that the operation will afford any 
relief. If the patient accepts, it should be only with this understanding 
and with the clear idea that it is as likely to be a useless as it is to be 
a useful procedure from his point of view. They can be promised, how- 
ever, that, if a subdural hematoma is found and if it is, as usual, fluid in 
type, it can be treated by drainage through the same opening. Further- 
more, they can be assured that, if present and treated, their chances for 
permanent relief of symptoms thereby are at least 3 out of 4, that the 
shorter the interval between the receipt of the injury and the drainage of 
the hematoma, the greater the chance of cure, and that the absence of 
other objective findings is of no significance since only about }^i of the 
cases that have been treated successfully in this way showed objective 
evidence of central nervous system disease in addition to their subjective 
symptoms. If a subdural hematoma is present and not removed, the pa- 
tient will not die but will become a chronic, permanent invalid and even- 
tually may end up in an insane asylum under the mistaken diagnosis of 
some form of non-organic psychosis. 

BIBLIOGRAPHY 

Books 

CANNON, WALTER B.: Traumatic Shock, D. Appleton and Co., New York, 
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COBB, STANLEY: A Preface to Nervous Disease, William Wood and Co., Balti- 
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COURVILLE, CYRIL B.: Pathology of the Central Nervous System, Pacific Press 
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Vol. VL 339 



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GUSHING, HARVEY: Studies in Intracranial Physiology and Surgery, Oxford 

Medical Publications, Oxford University Press, London, 1926. 
DAVIDOFF, LEO M. and DYKE, CORNELIUS G.: The Normal Encephalogram, 

Lea and Febiger, Philadelphia, 1937. 
FISHBERG, ARTHUR M.: Hypertension and Nephritis, Ed. 2, Lea and Febiger, 

Philadelphia, 1931. 
FORD, FRiANK, R. : Diseases of the Nervous System in Infancy, Childhood and 

Adolescence, Chas. C. Thomas, Baltimore, 1937. 
LEWIS, W. C. M.: A System of Physical Chemistry, Longmans, Green and Co., 

New York, 1923. 
MERRITT, H. H. and FREMONT-SMITH, F.: The Cerebrospinal Fluid, W. B. 

Saunders Co., Philadelphia, 1937. 
MUNRO, DON/\LD: Cranio-Cerebral Injuries, Oxford University Press, New 

York, 1938. 



Physio-Pathology 

CASSASA, CHARLES, S. B.: Multiple traumatic cerebral hemorrhages, Proc. 

N. Y. Path. Soc, N. S., 1924, XXIV, loi. 
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stasis: report of live cases with autopsy, Am. Jour. Med. Sc, 1929, 

CLXXVIII, 693. 
GUSHING, HARV'EY: Some experimental and clinical observations concerning 

states of increased intracranial tension, Am. Jour. Med. Sc, 1902, CXXIV, 

375- 

DANDY, W. E. : Experimental Hydrocephalus, Ann. Surg., 1919, LXX, 129. 

FORBES, H. S.: Cerebral circulation, observation and measurement of pial vessels. 
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FREMONT-SMITH, F. and KUBIE, L. S.: The relation of vascular hydrostatic 
pressure and osmotic pressure to the cerebro-spinal fluid pressure. The 
Proceed. Assoc, for Research in Nervous and Mental Disease, p. 104, vol. 
VIII, The Williams and Wilkins Co., Baltimore, 1929. 

LEARY, TIMOTHY: Subdural hemorrhages, Jour. Am. Med. Assoc, 1934, CHI, 

897. 

LeCOUNT, E. R. and APPLEBACH, CARL W.: Pathologic anatomy of trau- 
matic fractures of cranial bones and concomitant brain injuries. Jour. Am. 
Med. Assoc, 1920, LXXIV, 501. 

MARTLAND, H. S.: Punch drunk. Jour. Am. Med. Assoc, 1928, XCI, 1103. 

MARTLAND, H. S. and BELING, C. C: Traumatic cerebral hemorrhage, Arch. 
Neurol, and Psychiat., 1929, XXII, looi. 

MUNRO, D.: Cerebrospinal fluid pressure in the new-born, Jour. Am. Med. Assoc, 
1928, XC, 1688. 

MUNRO, D. and MERRITT, H. H.: The surgical pathology of subdural hema- 
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toniata. A study of 105 cases, Arch. Xeurol. and Psychiat., 1936, XXXV, 

64- 

\'ANCE, B. M.: Fractures of the skull: complications and causes of death: review 
of 512 necropsies and of 61 cases studied clinically. Arch. Surg., 1927, 
XIV, 1023. 

WEED, L. H.: The absorption of cerebrospinal fluid into the venous system, Am. 
Jour. Anat., 1923, XXXI, 191. 

WEED, L. H.: Experimental studies in intracranial pressure. The Proceed. Assoc, 
for Research in Nervous and Mental Disease, p. 25, \ol. VIII, The Williams 
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WEED, L. H.: Studies on cerebro-spinal fluid. II. The theories of drainage of 
cerebro-spinal fluid with an analysis of the methods of investigation. Jour. 
Med. Research, 1914-15, XXVI, 21; III. The pathways of escape from 
the subarachnoid spaces with particular reference to the arachnoid villi. 
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spinal fluid, Jour. Med. Research, 1914-15, XXVI, 93. 

WEED, L. H. and HUGHSON, W. : Intracranial venous pressure. Cerebrospinal 
fluid pressure as affected by the intravenous injection of solution of various 
concentrations. Am. Jour. Physiol., 1921, LVIII, loi. 

WEISS, SOMA: Syncope and Related Syndromes, Oxford Medicine, Oxford Uni- 
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Diagnosis 

AVER, J. B., DAILEY, M. E. and FREMONT-SMITH, F.: Denis-Ayer method 

for the quantitative estimation of protein in the cerebrospinal fluid. 

Arch. Neurol, and Psychiat., 1931, XXVI, 1038. 
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Jour. Surg., 1935, XXVIII, 34i- 
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Roent. and Radium Therapy, 1937, XXXVIII, 932. 
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cases. New Eng. Jour. Med., 1934, CCX, 1145. 
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Treatment 

BULLOCK, L. T., GREGERSEN, M. L and KINNEY, R.: The use of a hypertonic 
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DANDY, W. E. : Diagnosis and treatment of injuries of the head. Jour. Am. Med. 
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FAY, TEMPLE: Treatment of acute and chronic cases of cerebral trauma by 
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FOLEY, F. E. B.: Clinical uses of salt solution in conditions of increased intra- 
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FREMONT-SMITH, F., and MERRITT, H. H.: Influence of variations in fluid 
intake in intracranial pressure in "Epileptics", Arch. Neurol, and Psych., 
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GURDJIAN, E. S. : Studies on acute cranial and intracranial injuries, Ann. Surg., 
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HOLMAN, EMIL: Arteriovenous aneurysm, The Macmillan Co., New York, 1937. 

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MOORE, CHAS. H.: The diagnosis and treatment of the commoner forms of 
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and intracranial injury, Boston Med. and Surg. Jour., 1925, CXCIII, 1187. 

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MUNRO, D.: The operative removal of retained fragments of lumbar puncture 
and other needles. The Practitioner's Library', Blumer, G., Editor, Vol. V, 
Chapt. XI, p. 792, D. Appleton-Centur^' Co., New York, 1934. 

MUNRO, D. : The treatment of compound fractures of the skull. A study of 185 
cases, New Eng. Jour. Med., 1935, CCXIII, 551. 

MUNRO, D.: The activity of the urinary bladder as measured by a new and in- 
expensive cystometer. New Eng. Jour. Med., 1936, CCXIV, 617. 

MUNRO, D.: The treatment of the urinary bladder in cases with injury of the 
spinal cord. Am. Jour. Surg., 1937, XXXVIII, 120. 

MUNRO, D.: The emergency care of cranio-cerebral injuries, Am. Jour. Surg., 1937, 
XXXVIII, 739- 

MUNRO, D. : The surgical treatment of certain repeated explosive attacks of 
vertigo occurring in the absence of any demonstrable etiology — Meniere's 
disease. A report of fourteen cases of this and other types of aural vertigo 
and including one case involving both vestibular nerves. New Eng. Jour. 
Med., 1937, CCXVI, 539- 

MUNRO, D.: The diagnosis and therapy of so-called post-traumatic neurosis 
following cranio-cerebral injuries. In Press. 

MUNRO, D. and HAHN, J.: Tidal drainage of the urinary bladder. A pre- 
liminary report of this method of treatment as applied to "cord bladders" 
with a description of the apparatus, New Eng. Jour. Med., 1935, CCXII, 
229. 

WHITE, J. C. and WHITELAW, G. P.: Blood loss in neurosurgical operations, 
Ann. Surg., 1938, CVII, 287. 

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surgical patients, Ann. Surg., 1938, CVII, 438. 



The New-Born 

BAGLEY, CHAS.: Blood in the cerebro-spinal fluid. Arch. Surg., 1928, XVII, 18. 

CLIFFORD, STEWART H. and IRVING, F. C: Analgesia, anesthesia and the 
new-born infant, Surg. Gyn. and Obs., 1937, LXV, 23. 

DUNHAM, ETHEL C: The appraisal of the newborn infant, U. S. Dept. of Labor 
Bureau Pub., 242, Washington, D. C, 1938. 

EASTMAN, N. J.: Foptal blood studies; oxygen relationships of umbilical cord blood 
at birth, Bull. Johns Hopkins Hosp., 1930, XLVII, 221. Chemical nature of 
asphyxia neonatorum and its bearing on certain practical problems. Bull. Johns 
Hopkins Hosp., 1932, L, 39; Panel discussion on cyanosis in the new-born, 
Jour. Pediatrics, 1936, IX, 262; Role of anesthesia in production of as- 
phyxia neonatorum. Am. Jour. Obstet. and Gynec, 1936, XXXI, 563. 

LEFKOWITZ, L. L. : Extradural hemorrhage as the result of birth trauma. Arch. 
Pediat., 1936, LIII, 404. 

MUNRO, D.: Three cases of laryngeal spasm associated with intracranial hemor- 
rhage in the new-born, Ann. Otol. Rhin. and Laryng., 1925, XXXIV, 677. 
Vol. VI. 339 



BIBLIOGRAPHY 136 (65) 

MUNRO, D.: Cranial and intracranial damage in the new-born. An end result 
study of 117 cases, Surg. Gyn. and Obs., 1928, XLVII, 622. 

MUNRO, D.: Symptomatology and immediate treatment of cranial and intra- 
cranial injury in the new-born, including intracranial hemorrhage. New 
Eng. Jour. Med., 1930, CCIII, 502. 

MUNRO, D. and EUSTIS, R. S. : The diagnosis and treatment of intracranial 
hemorrhage in the new-born, Am. Jour. Dis. Child., 1922, XXIV, 273, 

Miscellaneous 

RADEMAKER, G. G. J.: Reactions Labyrinthiques et Equilibre: lAtaxie Laby- 

rinthique, Masson et Cie., Paris, 1935. 
SWIFT, G. W. : Cerebrocranial injuries: review of 190 cases. West. Jour. Surg., 

1932, XL, 343. 
Von STORCH, T. J. C, CARMICHAEL, E. A. and BANKS, T. E.: Factors 

producing lumbar cerebrospinal fluid pressure in man in the erect posture. 

Arch. Neurol, and Psychiat., 1937, XXXVIII, 11 58. 
Von STORCH, T. J. C. and SCHWAB, R. S.: Alterations of the cerebrospinal 

fluid subsequent to pneumoencephalography. New Eng. Jour. Med., 1937, 

CCXVII, 21. 
March i, 1939. 



Vol. VI. 339 



CHAPTER VI 
INTRACRANIAL TUMORS 

By Wilder Penfield and Donald McEachern 

Table of Contents 

Introduction 139* 

Intracranial Alterations Produced by Expanding Lesions 139 

Circulation of Cerebrospinal Fluid 139 

\'entricular Dilatation 142 

Effect upon the Brain of an Expanding Lesion 142 

Terminal Effects of Increased Pressure 144 

Increased Intracranial Pressure from other Causes than Tumor 146 

Effect of Hydration and Dehydration 146 

Cerebrospinal Fluid Alterations Produced by Brain Tumor 147 

Punctures 147 

Cerebrospinal Fluid Pressure 148 

Protein Content 149 

Cells in the Fluid 150 

Other Examinations 150 

Clinical Evidence of Increased Intracranial Pressure 151 

Headache 151 

Vomiting 152 

Papilledema 152 

Strabismus I54 

Enlargement of Head I55 

Convolutional Atrophy of Skull I55 

Thinning of the Clinoid Processes I55 

Signs of Acute Compression I55 

Localization I57 

Head Pain I57 

Epileptiform Seizures I57 

Neurological Examinations 161 

False Localizing Signs 162 

Localization by Simple Roentgenography 163 

Ventriculography and "Encephalography 171 

Technique ^7^ 

Interpretation ^74 

Arteriography I7° 

Syndromes Produced by Tumors Located in \'arious Parts of the Brain . 183 

Cerebellopontile Angle 184 

COPYRIGHT 1938 BY THE OXFORD UNIVERSITY PRESS, NEW YORK, INC. 

^37 



138 INTRACRANIAL TUMORS 

Cerebellum i88 

Pituitary and Suprasellar Region 190 

Frontal Lobe (Premotor) 195 

Rolandic Region 199 

Parietal Lobe (Post Sensory) 202 

Occipital Lobe 202 

Temporal Lobe 204 

Diencephalon 205 

Mesencephalon 206 

Pons and Medulla 208 

Dififerential Diagnosis 209 

Morbid Anatomy 212 

Encapsulated Tumors 212 

Structure of Meninges 212 

Structure of Perineuria! Sheath 212 

Meningeal Fibroblastoma 213 

Perineuria! Fibroblastoma 216 

Neurofibroma of von Recklinghausen 216(2) 

Pituitary Adenomas 216(5) 

Chromophole Adenoma 216(7) 

Chromophile Adenoma 216(7) 

Basophile Adenoma 216(7) 

Hypophyseal Duct Epitheliomas 216(8) 

Papillomas of the Choroid Plexus 216 (9) 

Hemangioblastomas and Hemangiomas 216(9) 

Cholesteatomas 216(12) 

Chordomas 216(13) 

Sarcomas 216(14) 

Sarcoma of the Dura 216(14) 

Sarcoma of the Leptomeninges 216(14) 

Melanotic Sarcoma 216(14) 

Metastatic Tumors of the Brain 216(14) 

Tuberculomas, Brain Abscesses and Syphilomas 216(16) 

Subdural Hematomas 216(16) 

Blood Cysts 216(16) 

Gliomas 216(17) 

Description of Neuroglia 216(17) 

Classification of Gliomas 216(17) 

Astrocytoma 216(17) 

Glioblastoma Multiforme 216(23) 

Medulloblastoma 216(27) 

Ependymoma 216(29) 

Astroblastoma 216(29) 

Spongioblastoma Polare T 216(29) 

Oligodendroblastoma and Oligodendroglioma 216(30) 

Neuroepithelioma 216(31) 

Pinealoma 216(32) 

General Observations on the Gliomas 216(32) 

Bibliography 216(36) 

Vol. VL 938 



ALTERATIONS PRODUCED BY EXPANDING LESIONS 139 

Introduction 

In the past the diagnosis of "brain tumor" has had a connotation as 
dreadful for the laity as that of "cancer" and "galloping consumption". 
Members of the medical profession also have shown a tendency to adopt 
an attitude of resignation; this attitude is no longer justified. Some 
brain tumors, it is true, give a hopeless prognosis, but other varieties 
are completely remediable. Handbook descriptions, which were formerly 
expressed in vague generalities, must be replaced by concise, detailed 
descriptions of tumor types, localizations and syndromes. 

The general practitioner must be alert to the fact that the child, who 
has been for a period of months cross and unsteady on his feet, may have 
a cerebellar tumor; the adult, who is deaf on one side and deviates to 
that side in walking, may well have a remediable, acoustic tumor, and 
the middle aged man, who has very rapidly increasing mental dullness and 
headache, quite possibly has an irremediable glioblastoma. 

Specialization has made possible great therapeutic advances. Pneu- 
mography as a preliminary to operation has substituted certainty of local- 
ization for presumptive diagnosis. But this has made the neurologist's 
counsel all the more important and instruction of the practitioner all the 
more urgent. It has converted the patella hammer and the ophthal- 
moscope into effective instruments that point less often to interesting 
anomalies and more often to constructive therapy. 

Intracranial Alterations Produced by Expanding Lesions 

Obviously a tumor growing within the skull must produce increased 
intracranial pressure because of the fact that the skull is a closed box. 
The expanding lesion compresses the brain and disturbs the circulation 
of cerebrospinal fluid and of blood through and about the brain. The 
mechanism of these disturbances is common to all types of tumor and is 
now described in brief outline. This mechanism must be studied in order 
to understand the effects of tumor growth and the ventricular displace- 
ment as shown by ventriculography. 

Circulation of Cerebrospinal Fluid 

Under normal conditions cerebrospinal fluid is formed within the 
choroid plexuses in the lateral ventricles of the brain. It flows into the 
third ventricle and down the aqueduct of Sylvius into the fourth ven- 
tricle (Fig. i) and out into the cisterna magna and basal subarachnoid 

Vol. VI. 938 



140 



INTRACRANIAL TUMORS 



cisternae (C and BC, Fig. 2). From the cisterna magna some fluid passes 
outward over the cerebellum to be absorbed into the subarachnoid veins 
there, but most of it passes forward and upward through the basal cis- 
ternae to the interpeduncular cisterna from which it flows into the fissures 
of Sylvius and bathes the surface of the cerebral hemispheres. There it 




KiG. I. Schematic representation of the ventricles in relation to falx (F) and ten- 
torium (T). FM, foramen of Monro; III, third ventricle; AS, aqueduct of Sylvius; 
LV, lateral ventricle; IV, fourth ventricle. 

is reabsorbed into the blood stream through the walls of the veins within 
the subarachnoid space and into the dural sinuses through the pacchi- 
onian granulations. 

Increase of intracranial pressure results whenever formation of cere- 
brospinal fluid exceeds the rate of its absorption. Under normal condi- 
tions an increase of fluid pressure results in an increased rate of absorp- 
tion. Mortensen and Weed^^ have shown that compression of the vein 

Vol. VI. 938 



CIRCULATION OF CEREBROSPINAL FLUID 



141 



of Galen or of the lateral sinus may cause congestion of the choroid plexus 
and increased formation of cerebrospinal fluid, but they point out that 
increase of intracranial pressure does not result unless absorption is im- 
paired also. 

In general, the all-important regulator of the cerebrospinal fluid 
pressure is the rate of absorption of the fluid. Consequently the pres- 




FlG. 2. Sagittal section through skull and longitudinal sinus (S) to show relation of 
falx and tentorium (T) to right half of brain. SP, septum pellucidum; FM, right fora- 
men of Monro; III, third ventricle; AS, aqueduct of Sylvius; IV, fourth ventricle; 
CM, cisterna magna; BC, cisterna basalis, the upper portion being the cisterna inter- 
peduncularis; P, pituitary gland; V'G, great vein of Galen; I. Tent., dotted outline of 
incisura of tentorium beyond brain stem; For. Mag., foramen Magnum. 

sure may be increased by obstruction to the circulation of the fluid at 
any point between its origin in the ventricles and its absorption in the 
subarachnoid space over the vault. 



\'oL. VI. 938 



142 INTRACRANIAL TUMORS 

Ventricular Dilatation 

A relatively small expanding lesion within the cerebellum or in the 
cerebello-pontile angle shuts off escape of cerebrospinal fluid down the 
aqueduct of Sylvius (AS, Fig. i) and consequently the pressure within 
the ventricles, which lie above, rises to a figure which may be as high as 
from 400 to 700 mm. of water. This high pressure produces hydroce- 
phalic ventricular dilatation and generalized increase of intracranial 
pressure. Thus a small tumor in this strategic situation produces earlier 
pressure increase than would the same sized lesion above the tentorium. 
Curiously enough, however, an infiltrating neoplasm of the pons and 
medulla oblongata is rather slow to shut off the fluid escape. 

Obviously an expanding lesion in the vicinity of the third ventricle 
may produce dilatation of the lateral ventricles, and such a lesion placed 
close to one foramen of Monro may occlude it and cause dilatation of the 
corresponding lateral ventricle. 

Effect upon the Brain of an Expanding Lesion 

A slowly expanding lesion within or upon one cerebral hemisphere 
can displace the brain a considerable distance with little increase of 
intracranial pressure and with little disturbance of function at first. 
Slowly increasing pressure upon brain, whether from tumor or ventricle, 
causes it to decrease in volume, as though it melted, with remarkably 
little disturbance of function. This decrease in tissue volume takes place 
chiefly in the white matter, and collateral branches are probably sacri- 
ficed while essential axones are preserved^^. 

An expanding lesion placed anywhere in one cerebral hemisphere in 
such a position as not to obstruct a ventricle directly eventually will 
increase intracranial pressure, but not equally so, throughout the cranial 
cavity. The pressure upon or within the affected hemisphere exceeds 
that of the opposite hemisphere or the cerebellum because of the resis- 
tance offered by the cerebral tissue and by the falx and tentorium. The 
falx is quite rigid enough to subdivide the cranial box into two lateral 
compartments, and the tentorium still more effectively separates off the 
posterior fossa of the skull into a third compartment (Figs. 3 and 5). 

But the pressure within the affected hemisphere has a distant effect 
upon the aqueduct of Sylvius which lies within the incisura of the ten- 
torium (Fig. 4). It tends to collapse the aqueduct so that cerebrospinal 
fluid can only escape down this channel when forced by increased pressure 
in the ventricles. This back pressure, although not as great as in the case 
\'oL. VI. 938 



ALTERATIONS PRODUCED BY EXPANDING LESIONS 143 

of complete obstruction, nevertheless tends to dilate the ventricles. Less 
dilatation takes place on the ipsilateral side (Fig. 5), for the pressure of 
the tumor within that hemisphere resists ventricular dilatation more ef- 
fectively than the somewhat lower pressure within the other hemisphere. 



Fig. 3. The dural partitions within the skull to show how the aqueduct of Sylvius 
(S) carries fluid down through the incisura tentorii and how the cisterna basalis (B) brings 
the fluid back to the cisterna interpeduncularis (C), whence it is distributed over the 
surface of the cerebral hemispheres to be absorbed. 

As expansion continues the structures of the hemisphere which is 
being compressed begin to herniate under the falx into the opposite half 
of the cranial chamber (Figs. 18 and 19). The aqueduct now is pressed 
upon more severely, and the intraventricular pressure mounts rapidly. 
Dilatation of the opposite ventricle, which has been gradual up to this 
point, progresses at increased pace and signs of increased intracranial 
pressure become acute. 

Vol. VI. 938 



144 



INTRACRANIAL TUMORS 



Terminal Effects of Increased Pressure 

If the tumor expands rapidly, the brain does not melt away. It is 
compressed with consequent loss of function, and events lead swiftly to 
death. Slow expansion may be converted suddenly into rapid expansion 




Fig. 4. Drawing of the base of the skull with the tentorium in place to show the 
relation of midbrain, aqueduct of Sylvius (S) and cisterna interpeduncularis (A) to the 
incisura tentorii (B). (.'\fter Penfield, 1935.) 

Vol. VI. 938 



TERMINAL EFFECTS OF INCREASED PRESSURE 145 

by hemorrhage into the substance of a tumor or by rapid cyst forma- 
tion. But whether the evolution is slow or fast, the following phenomena 
appear eventually. The high pressure compresses the intracranial veins and 
thus impedes the outflow of blood from the brain. The resulting increase in 
venous pressure allows reabsorption of fluid into the veins only at a higher 
fluid pressure. In addition, the increase of venous pressure in the choroid 




Fig. 5. Schematic frontal transection of cranium to show falx tentorium and dural 
sinuses. (After Penfield, 1934.) 

plexus results in more forceful formation of cerebrospinal fluid and thus 
establishes a vicious circle of mounting pressure. 

The brain then tends to be forced from the cranial cavity by the 
only existing outlets, the incisura of the tentorium (Figs. 2 and 4) and 
the foramen magnum (Fig. 2). Herniation through the incisura produces 
ischemia of the mesencephalon which results in coma and paralysis of 
the third cranial nerve. Herniation of the cerebellum downward into 
the foramen magnum may also occur, especially if the expanding lesion 
is situated in the posterior fossa, and this produces ischemia of the me- 
dulla oblongata resulting in arrest of respiration preceded by Cheyne- 
Stokes breathing. For clinical signs of compression the reader is referred 
to the Section further along on Clinical Evidence of Increased Intra- 
cranial Pressure. Obviously cisternal puncture is very dangerous, and 
lumbar puncture, if done recklessly, may precipitate bulbar paralysis by 
withdrawing the support exerted by the cerebrospinal fluid pressure 

Vol. VI. 938 



146 INTRACRANIAL TUMORS 

below. Even in the absence of such precipitating factors respiratory 
arrest may occur with startling suddenness in patients with high intra- 
cranial pressure. 

Increased Intracranial Pressure from other Causes than Tumor 

Although brain tumor is the most frequent cause of a continuing in- 
crease of intracranial pressure, other causes must be recognized. These 
include premature closure of the sutures occurring in childhood before the 
growth of the brain has ceased (oxycephaly), thickening of the inner 
surface of the skull, as in Paget's disease, subdural hematoma, pacchy- 
meningitis hemorrhagica interna, brain abscess, internal hydrocephalus 
due to adhesive closure of the subarachnoid spaces or to chronic meningi- 
tis, tuberculous, syphilitic etc., or congenital malformations etc. So-called 
otitic hydrocephalus, which in reality usually means a subdural efifusion 
of fluid secondary to an inflammatory process in the mastoid, may also 
produce an increase of pressure without localizing signs. Furthermore, a 
continuing increase of intracranial pressure may occur, though rarely, as 
a result of cerebral edema in encephalitis lethargica, Schilder's encepha- 
litis, lead intoxication and cerebral trauma. 

Effect of Hydration and Dehydration 

Weed and McKibben'-^ were the first to show that changes in the 
osmotic pressure of the blood greatly modify the bulk of the brain and 
the pressure of cerebrospinal fluid. Intrav^enous injection of a hypotonic 
solution, e.g., distilled water, causes increased formation and decreased 
absorption of cerebrospinal fluid, the brain swells and intracranial pres- 
sure rises. Conversely, injection of hypertonic solution, e.g., 15 per cent, 
sodium chloride solution, causes the brain to shrink and lowers the intra- 
cranial pressure. These factors are of great importance in the manage- 
ment of increased intracranial pressure. Measures leading to hydration 
of the blood, e.g., large amounts of water by mouth, hypotonic solutions 
by rectum, are contraindicated. Measures leading to dehydration, e.g., 
saline cathartics, administration of hypertonic solutions intravenously or 
by rectum, are known to benefit the symptoms of increased intracranial 
pressure. 

Magnesium sulphate may be given every four hours by mouth, 5iss (45 
gm.) of the crystals in 5 viii (240 c.c.) of water, or by rectum, ^ iii (90 gm.) of 
the crystals in 5vi (180 gm.) of water, until the intracranial pressure has 
been lowered effectively. Hypertonic solutions introduced intravenously 

Vol. VI. 938 



CEREBROSPINAL FLUID ALTERATIONS 147 

act more quickly. Glucose, 50 to 100 c.c. of 50 per cent, solution, is su- 
perior to hypertonic sodium chloride in producing a sustained, several 
hours, fall of intracranial pressure with less tendency to a subsequent rise 
exceeding the initial pressure. Results seem to indicate that the use of 
sucrose as suggested by Bullock, Gregersen and Kinney^'' is even more ef- 
fective for the cont/ol of increased intracranial pressure. One hundred to 
200 c.c. of 50 per cent, solution may be given intravenously. Sucrose is 
excreted unchanged in the urine and, therefore, has no nutritive value. 
The above measures have but a temporary effect, and for this reason 
are used chiefly in cases of brain tumor as part of the preoperative prepa- 
ration and postoperative treatment. 

Cerebrospinal Fluid Alterations Produced by Brain Tumor 

Examination of the cerebrospinal fluid is at times helpful in the diag- 
nosis and even in the localization of intracranial tumors. The subject is 
dealt with in general elsewhere (Vol. VI, Chapt. XL), and we refer here 
only to specific points. The reader also may amplify his information on 
this subject by reference to Greenfield'''^ and to the exhaustive studies of 
Hare^^ and Fremont-Smith^", who respectively have reported their find- 
ings in 186 and 164 cases of verified cerebral tumors. 

Punctures 

The fluid usually is drawn from the lumbar region and less commonly 
from the cisterna magna or lateral ventricle. The fluids obtained from 
these regions differ somewhat even in the normal individual. In case of 
tumor they may differ widely in pressure and constitution, and these dif- 
ferences may assist in determining both the location and type of tumor. 

Lumbar puncture is a hazardous procedure in the presence of increased 
intracranial pressure due to tumor and should be omitted unless the evi- 
dence is essential. Although the danger may be exaggerated, the greatest 
caution should be employed, especially if a neoplasm of the posterior fossa 
is suspected. In this case lumbar puncture should be omitted and fluid 
obtained from the ventricle, if at all. For lumbar puncture a small 
bore needle should be used, and fluid, not exceeding a few cubic centi- 
meters, should be removed drop by drop with the patient in the horizontal 
position. If signs of respiratory embarrassment or significant changes in 
blood pressure or pulse rate occur, the procedure should be terminated. 

Combined ventricular and lumbar puncture as recommended by 
Fremont-Smith and Hodgson^^ is safer than lumbar puncture in cases 

Vol. VI. 938 



148 INTRACRANIAL TUMORS 

with high intracranial pressure and yields more information. Ventric- 
ular puncture alone probably is still safer, but it should be remembered 
that syphilis cannot be excluded by examination of ventricular fluid 
which may prove quite normal, while the lumbar fluid shows the changes 
characteristic of syphilis. 

Abnormalities of cerebrospinal fluid in the presence of cerebral tumor 
are related to a number of factors. These include the proximity of neo- 
plasm to ventricle or leptomeninges, its size, type and vascularity as well 
as the amount of hemorrhage and degeneration associated with it. 

Cerebrospinal Fluid Pressure 

The normal pressure for the adult in the lateral recumbent position 
ranges between 120 and 170 mm. of cerebrospinal fluid. It is slightly 
less than this in the child. Pressure of over 200 mm. generally is looked 
upon as abnormal. Pressure of 500 mm. or higher sometimes is found 
in cases of intracranial tumor. The pressure was higher than normal 
in over 70 per cent, of Fremont-Smith's cases of brain tumor. 

A normal pressure in no way excludes tumor. A persistently elevated 
pressure or one that is rising, as determined by repeated punctures, is 
strongly in favor of tumor. Increased pressure may be present, however, 
for several months before the appearance of papilledema. It should be 
remembered that vomiting, diarrhoea and other causes of dehydration 
may lower an otherwise high pressure, and conversely procedures leading 
to hydration may elevate it. Both ether and morphine tend to elevate 
the pressure. 

Measurement of pressure with the patient in the sitting posture, as 
before encephalography, is unsatisfactory. In this position the fluid in a 
glass manometer (Ayer) usually rises to about 10 cm. below the top of 
the patient's head (Fig. 13). Anything above this level may be consid- 
ered abnormally high. 

Occasionally lumbar puncture pressure may be within normal limits, 
although the intracranial pressure actually is high. This may be due to 
blockage of the downward flow of fluid and would indicate that with- 
drawal of fluid may be dangerous. Furthermore, a slowly expanding 
lesion, such as a slowly growing tumor or subdural hematoma, may allow 
temporary readjustment of the whole brain so that the pressure may be 
normal temporarily. 

It has been pointed out elsewhere in this chapter that there are many 
causes of increased pressure other than intracranial tumor, e.g., menin- 
gitis, subarachnoid hemorrhage, vascular hypertension especially when 

Vol. VI. 938 



PROTEIN CONTENT OF SPINAL FLUID 149 

associated with uremia, oxycephaly, etc. Elevation of cerebrospinal fluid 
pressure must, therefore, be evaluated along with other clinical evidence. 

Protein Content 

Quantitative determination of the total protein content of the cere- 
brospinal fluid is of great importance in cases of suspected brain tumor. 
The upper limits of normal are 45 mgm. per cent, for lumbar fluid, 25 
mgm. per cent, for cisternal fluid and 15 mgm. per cent, for fluid from 
the lateral ventricle. Although qualitative tests of globulin, Pandy, 
frequently parallel the increase of total proteins, they are but a rough 
guide. In Hare's series the lumbar fluid showed an elevation of protein 
in 61 per cent, of cases of meningeal fibroblastoma and in 65 per cent, of 
cases of glioblastoma multiforme. All cases of perineurial fibroblastoma 
of the VIII nerve and other tumors of the cerebello-pontine angle showed 
an increased protein. An increase occurred in 35 per cent, of astro- 
cytoma cases, when the tumor was above the tentorium, but in no in- 
stances, when it was subtentorial. Fremont-Smith's study showed that 
the lumbar fluid protein is above normal in 70 per cent, of all cases of 
brain tumor. It is higher than 100 mgm. per cent, in about 30 per cent., 
but the value rarely exceeds 500 mgm. per cent. 

It is generally considered that the increased protein is due to tran- 
sudation from blood vessels or from degenerating areas in the tumor or 
possibly from surrounding areas of edema. An increase, therefore, is 
likely to occur, if the tumor is especially vascular, if it is rapidly growing 
and malignant, and if it is near to, or invades, the ventricular system. In 
tumors of the cerebello-pontine angle the increase of protein probably is 
due, in part, to block and stagnation of fluid in the lumbar sac and also to 
seepage from congested vessels in or around the tumor. A tumor in the 
cerebral hemisphere seldom causes an increase in protein unless it lies 
deep and invades the ventricular system. 

Merritt and Fremont-Smith^^ have discussed the relation of the pro- 
tein content of ventricular fluid to that of the lumbar fluid. If the 
lumbar fluid protein is normal, that in the lateral ventricles also is nor- 
mal. A tumor invading one lateral ventricle causes an increase of protein 
in the fluid from that ventricle, while fluid from the opposite ventricle is 
normal. Tumor of the corpus callosum, of the third ventricle or multiple 
metastatic tumors may cause high protein in the fluid from both lateral 
ventricles. In posterior fossa tumors the fluid from both lateral ventricles 
is normal. 

Increase of protein in the cerebrospinal fluid is, of course, a common 

Vol. VI. 938 



I50 INTRACRANIAL TUMORS 

finding in many conditions other than tumor which affect the central 
nervous system. Bleeding into the subarachnoid space may of itself 
cause an elevation of protein due to dilution of blood proteins in the 
cerebrospinal fluid. For each i,ooo red blood cells per cu. mm. of cere- 
brospinal fluid there is an increase of about I mgm. per cent, of protein. 
A protein content out of all proportion to the amount of blood present 
might be evidence of tumor. Xanthochromia is said to occur in about 
15 per cent, of tumor cases and usually is associated with considerable 
increase of protein, although occasionally it may result from blood pig- 
ment derived from extravasations of blood too small to elevate the pro- 
tein. 

Cells in the Fluid 

Increase of leucocytes in the cerebrospinal fluid is rare in cases of 
cerebral neoplasm. Only 9 per cent, of Hare's cases showed a cell count 
above 10 per cu. mm. Counts up to several thousand have been de- 
scribed, however, and when acute degeneration or hemorrhage takes place 
within an infiltrating tumor, large numbers of polymorphonuclear leuco- 
cytes may be found in the spinal fluid. Cerebral abscess occasionally is 
associated with pleocytosis, as are rare granulomata. 

Red blood cells usually are not present. In rare instances extravasa- 
tion of blood may occur in amounts varying from microscopic to massive 
hemorrhage. In the latter event the picture may be indistinguishable 
from that of spontaneous subarachnoid hemorrhage due to simple vascular 
lesions. Russel and Kershman'"^ have described sudden, gross, subarach- 
noid hemorrhage in three cases of cerebral tumor. 

When cells are present in the fluid, they should be studied carefully 
and if there is any doubt as to their nature, the fluid should be centri- 
fuged, and the sediment embedded in celloidin, for metastasis occurs 
through the spinal fluid in certain gliomas as described in the section on 
Morbid Anatomy, and we have made the diagnosis in this manner. 

Other Examinations 

The Wassermann reaction of the blood and, if safe, of the lumbar 
fluid should be determined in all cases of suspected brain tumor. It is 
not only necessary to exclude syphilis as a cause of symptoms, but it is 
also necessary to remember that a neoplasm and syphilis may coexist. 

Other types of examination are of little or no value. There is no 
characteristic colloidal gold curve, and when real precipitation occurs, in 
Vol. VI. 938 



EVIDENCE OF INCREASED INTRACRANIAL PRESSURE 151 

about 35 per cent, of cases, usually it is in the middle zone and due to 
the high protein content of the fluid. The sugar and chloride values 
usually are normal, although occasionally they are altered due to general 
metabolic upset, e.g. hyperglycemia, lowered plasma chloride due to 
vomiting, etc. 

Clinical Evidence of Increased Intracranial Pressure 

It is convenient to divide the evidences of intracranial tumor into 
those that are general and attributable to increased intracranial pressure 
and those that are focal and produced by the local effect of the growth. 
The first group is treated in this section and the second group in the next 
section, that on Localization. Despite the improved x-ray methods for 
recognizing tumors in the earlier stages, it must be confessed that the 
clinical diagnosis is made in many instances only after the onset of in- 
creased intracranial pressure, about 70 per cent. Occasionally the intra- 
cranial pressure remains normal even when a large tumor is present. 
This may occur, if the expansion of the tumor has been slow enough to 
allow complete readjustment of the brain to its presence. 

Headache, vomiting and papilledema are the cardinal signs of gener- 
alized increase of intracranial pressure. In a series of cerebral tumors 
reported by Brain'- headache occurred in 88 per cent., papilledema in 
75 per cent, and vomiting in 65 per cent. All three manifestations oc- 
curred together in 60 per cent, of the cases. To this triad should be added 
other signs, particularly strabismus, as will be described below. 

Headache 

Simple increase of intracranial pressure usually gives rise to frontal 
headache, although an expanding lesion in the posterior fossa of the skull 
may cause reference of the ache into the occipital and posterior cervical 
regions. The headache usually is dull, often throbbing and made worse by 
exertion and stooping. In young children often there is no complaint of 
headache, but the parents are apt to observe that the child has become 
bad-tempered. Severe headache, which comes on very suddenly and may 
be precipitated or relieved by change of head posture, sometimes is pro- 
duced by a movable or pedunculated tumor within one ventricle which 
blocks one foramen of Monro or the aqueduct of Sylvius intermittently 
by ball-valve action. 

Certain other types of headache must be differentiated from the 
above. Migraine, which is associated at times with vomiting, is more 
Vol. VL 938 



152 INTRACRANIAL TUMORS 

apt to be episodic and has certain characteristic features. It is re- 
lated to emotional stress and, in women, usually is related to the men- 
strual cycle. It is often familial and first makes its appearance at the 
time of puberty. An attack is apt to be ushered in with a sense of fa- 
tigue and with visual phenomena such as lights and figures before the 
eyes. Photophobia may appear during an attack. The localization usu- 
ally is behind one eye, but it may be bilateral. Ergotamine tartrate 
administered at the onset usually succeeds in aborting an attack, if the 
condition is true migraine. 

Headaches due to eye strain ordinarily are localized in or near the 
eyes. They are apt to be made worse by reading and especially by watch- 
ing cinematographic performances. A post-traumatic headache usually is 
more constant and more influenced by p